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<h1>Aspirin, brain, and cancer</h1>
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<div style="text-align: center;">
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<a href="/"><img class="epic" src="/icons/chads/chad.png"></a>
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<hr>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
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<p>From the <a href="https://raypeat.com/articles/aging/aspirin-brain-cancer.shtml" target="_blank">original article</a> in 2006. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
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<p>
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<em>Since
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the 1970s, aspirin has been thought of as an inhibitor of prostaglandin
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synthesis, but that is only part of its effect. Sometimes its effect
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is the opposite of the effects of other prostaglandin inhibitors.</em></p>
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<p><em>It
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protects against the harmful effects of estrogen,
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prolactin, serotonin, cortisol, histamine, and radiation
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(u.v., x-rays, gamma rays).</em></p>
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<p><em>It
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prevents cancer, and can cause its regression. It inhibits vascular
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proliferation. It inhibits interleukin 6 (and other inflammatory
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cytokines), which is a factor in heart disease and breast and liver
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cancer.</em></p>
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<p><em>It
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protects the brain, and can improve learning. It's an antioxidant, prevents
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cataracts, and protects against glycation in diabetes. </em></p>
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<p><em>It
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prevents premature birth and prevents birth defects caused by diabetes,
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preeclampsia, and exposure to alcohol. It prevents recurrence of neural
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tube defects and protects against many of the
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gestational problems associated with lupus.</em></p>
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<p><em>Although
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aspirin protects against uncontrolled cell proliferation, as in cancer
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and psoriasis, salicylic acid increases normal cell division in the
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skin.</em></p>
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<p><em>Aspirin
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protects against many forms of shock and
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stess, and corrects imbalances in the nervous system.</em></p>
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<p><em>It protects against several
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kinds of toxins involved in brain degeneration.</em></p>
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<p><em>"Aspirin
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elevated ATP levels not only in intact cortical neurons but also in
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isolated brain mitochondria, an effect concomitant with an increase
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in NADH-dependent respiration by brain
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submitochondrial particles."</em></p>
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<p><em>
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De Cristobal, et al., 2002</em></p>
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<p><em>"The
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pharmacological action of salicylate cannot be explained by its inhibition
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of cyclooxygenase (COX) activity." ". . .
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salicylate exerts its antiinflammatory action in part by suppressing
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COX-2 induction. . . ."
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XM Xu, et al., 1999</em></p>
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<p>
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When
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a drug such as caffeine or aspirin turns out to have a great variety
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of protective effects, it's important to understand what it's doing. </p>
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<p>Because
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aspirin has been abused by pharmaceutical companies that have competing
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products to sell, as well as by the original efforts to promote aspirin
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itself, people can easily find reasons why they shouldn't take it.</p>
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<p>Early
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in the 20th century, people were told that fevers were very bad, and
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that aspirin should be used whenever there is a fever.</p>
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<p>In
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the 1980s, there was a big publicity campaign warning parents that giving
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aspirin to a child with the flu could cause the potentially deadly Reye
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syndrome. Aspirin sales declined sharply, as sales of acetaminophen
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(Tylenol, etc.) increased tremendously. But in Australia, a study of
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Reye syndrome cases found that six times as many of them had been using
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acetaminophen as had used aspirin. (Orlowski, et al., 1987) </p>
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<p>Until
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the 1950s and 1960s, when new products were being promoted, little was
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said about the possibility of stomach ulceration from aspirin. Lately,
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there has been more publicity about the damage it can do to the stomach
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and intestine, much of it in connection with the sale of the new "COX-2
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inhibitors." (These new drugs, rather than protecting the circulatory
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system as aspirin does, damage it.) Aspirin rapidly breaks down into
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acetic acid and salicylic acid (which is found in many fruits), and
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salicylic acid is protective to the stomach and intestine, and other
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organs. When aspirin was compared with the other common antiinflammatory
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drugs, it was found that the salicylic acid it releases protects against
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the damage done by another drug. (Takeuchi, et al, 2001; Ligumsky, et
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al., 1985.) Repeated use of aspirin protects the stomach against very
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strong irritants. The experiments in which aspirin produces stomach
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ulcers are designed to produce ulcers, not to realistically model the
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way aspirin is used.</p>
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<p>Recently,
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the public has been led to believe that drugs are being designed to
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fit certain cellular "receptors." The history of the "COX-2
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inhibitors" is instructive, in a perverse way. The structures of
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DES and other synthetic estrogens were said to relate to "the estrogen
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receptor." Making these estrogenic molecules more soluble in water
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made them somewhat anti-estrogenic, leading to products such as Tamoxifen.
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But some of the molecules in this group were found to be antiinflammatory.
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The structure of Celecoxib and other "COX-2 inhibitors" is
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remarkably similar to the "designer estrogens." Considering
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this, it's a little odd that so few in the U.S. are openly discussing
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the possibility that estrogen's function is directly related to inflammation,
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and involves the production of many inflammatory mediators, including
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COX-2. (See Lerner, et al., 1975; Luo, et al., 2001; Cushman, et al,
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2001; Wu, et al., 2000; Herrington, et al., 2001.)</p>
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<p>Soot
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and smoke contain many chemicals that produce inflammation (Brune, et
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al., 1978). In the 1930s, soot was known to be both carcinogenic and
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estrogenic, and analysis of its components led to the production of
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the early commercial estrogens. Any intelligent person reading the chemical
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and biological publications of that time will see how closely associated
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cancer, inflammation, and estrogen are.</p>
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<p>Soon
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after vitamin E was discovered, tocopherol was defined as a brain-protective,
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pregnancy protective, male fertility protective, antithrombotic, antiestrogenic
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agent. But very soon, the estrogen industry made it impossible to present
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ideas that explained vitamin E, progesterone, vitamin A, or thyroid
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hormone in terms of the protection they provide against estrogenic substances.
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Since the polyunsaturated fats caused the same conditions that were
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caused by unopposed estrogen, vitamin E came to be known as an "antioxidant,"
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because it reduced their toxicity. (Vitamin E is now known to
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suppress COX-2, synergizing with aspirin and opposing estrogen.)</p>
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<p>In
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1970, when I was beginning to see the ways in which unopposed estrogen
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and accumulated polyunsaturated fats interacted with a vitamin E deficiency
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during aging and in infertility, I got some prostaglandins to experiment
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with, since they are products of the oxidation of linoleic acid. The
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prostaglandins are an interesting link between estrogens and inflammation,
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in normal physiology as well as in disease.</p>
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<p>I
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wanted to test their effects on the uterus, especially the sites where
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the embryos implant. There was a theory that the electrical charge of
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the surface of the uterus was decreased at the implantation sites, to
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reduce the repulsion between two negatively charged things. Although
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there were regions of lower surface charge along the lining of the uterus,
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the charge changed as waves of muscle contraction moved along the uterus,
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and the prostaglandins affected the contractions.</p>
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<p>To
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understand the differences between the different types of prostaglandin,
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I tested them on my arm, and those with the most hydroxyl groups produced
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regions with an increased negative charge. For comparison, I exposed
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another spot to sunlight for an hour, and found that there was a similar
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increase in the negative charge in that spot. Apparently the prostaglandins
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were causing an injury or excitation, a mild inflammation, in the skin
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cells.</p>
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<p>A
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few years later, aspirin was found to inactivate the enzyme that forms
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prostaglandins, by the transfer of the acetyl radical to the enzyme.
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This became the orthodox "explanation" for what aspirin does,
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though it neglected to explain that salicylic acid (lacking the acetyl
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radical) had been widely known in the previous century for its very
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useful antiinflammatory actions. The new theory did explain (at least
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to the satisfaction of editors of medical magazines) one of aspirin's
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effects, but it distracted attention from all the other effects of aspirin
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and salicylic acid.</p>
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<p>Aspirin
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is an antioxidant that protects against lipid peroxidation, but it also
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stimulates mitochondrial respiration. It can inhibit abnormal cell division,
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but promote normal cell division. It can facilitate learning, while
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preventing excitotoxic nerve injury. It reduces clotting, but it can
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decrease excessive menstrual bleeding. These, and many other strangely
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beneficial effects of aspirin, strongly suggest that it is acting on
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very basic biological processes, in a coherent way.</p>
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<p>In
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explaining aspirin's effects, as in explaining those of estrogen and
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progesterone, or polyunsaturated fats and vitamin E, I think we need
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concepts of a very broad sort, such as "stability and instability." </p>
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<p>The
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COX (cyclooxygenase) enzymes, that make prostaglandins, are just one
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system among many that are activated by stress. Aromatase, that makes
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estrogen, enzymes that make histamine, serotonin and nitric oxide, the
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cytokines, and the stress-induced hormones of the pituitary and adrenal
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glands, are turned on in difficult situations, and have to be turned
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off when the threat has been overcome. The production of energy is the
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basis for overcoming all threats, and it has to be conserved in readiness
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for future needs.</p>
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<p>The
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fetus produces saturated fats such as palmitic acid, and the monounsaturated
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fat, oleic acid, which can be turned into the Mead acid, ETrA (5,8,11-eicosatrienoic
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acid), and its derivatives, which are antiinflammatory, and some of
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which act on the "bliss receptor," or the cannibinoid receptor.
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In the adult, tissues such as cartilage, which are protected by their
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structure or composition from the entry of exogenous fats, contain the
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Mead acid despite the presence of linoleic acid in the blood.</p>
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<p>At
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birth, the baby's mitochondria contain a phospholipid, cardiolipin,
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containing palmitic acid, but as the baby eats foods containing polyunsaturated
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fatty acids, the palmitic acid in cardiolipin is replaced by the unsaturated
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fats. As the cardiolipin becomes more unsaturated, it becomes less stable,
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and less able to support the activity of the crucial respiratory enzyme,
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cytochrome oxidase.</p>
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<p>The
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respiratory activity of the mitochondria declines as the polyunsaturated
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oils replace palmitic acid, and this change corresponds to the life-long
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decline of the person's metabolic rate.</p>
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<p>In
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old age, a person's life expectancy strongly depends on the amount of
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oxygen that can be used. When the mitochondria can't use oxygen vigorously,
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cells must depend on inefficient glycolysis for their energy. </p>
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<p>Estrogen
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activates the glycolytic pathway, while interfering with mitochondrial
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respiration. This resembles the aged or stressed metabolism, in which
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lactic acid is produced instead of carbon dioxide.</p>
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<p>Aspirin
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activates both glycolysis and mitochondrial respiration, and this means
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that it shifts the mitochondria away from the oxidation of fats, toward
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the oxidation of glucose, resulting in the increased production of carbon
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dioxide. Its action on the glycolytic enzyme, GAPDH, is the opposite
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of estrogen's.</p>
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<p>The
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shift away from fat oxidation under the influence of aspirin doesn't
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lead to an accumulation of free fatty acids in the circulation, since
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aspirin inhibits the release of fatty acids from both phospholipids
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and triglycerides. Estrogen has the opposite effects, increasing fat
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oxidation while increasing the level of circulating free fatty acids,
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since it activates lipolysis, as do several other stress-related hormones.</p>
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<p>The
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polyunsaturated fatty acids, such as linolenic, linoleic, arachidonic,
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EPA, and DHA, have many directly toxic, antirespiratory actions, apart
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from the production of the prostaglandins or eicosanoids. Just by preventing
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the release of these fatty acids, aspirin would have broadly antiinflammatory
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effects.</p>
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<p>Since
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the polyunsaturated fats and prostaglandins stimulate the expression
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of aromatase, the enzyme that synthesizes estrogen, aspirin decreases
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the production of estrogen. So many of aspirin's effects oppose those
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of estrogen, it would be tempting to suggest that its "basic action"
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is the suppression of estrogen. But I think it's more likely that both
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estrogen and aspirin are acting on some basic processes, in approximately
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opposite ways. </p>
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<p>Bioelectrical
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functions, and the opposition between carbon dioxide and lactic acid,
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and the way water is handled in cells, are basic conditions that have
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a general or global effect on all of the other more specific biochemical
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and physiological processes. Originally, estrogen and progesterone were
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each thought to affect only one or a few biochemical events, but it
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has turned out that each has a multitude of different biochemical actions,
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which are integrated in globally meaningful ways. The salicylic acid
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molecule is much smaller and simpler than progesterone, but the range
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of its beneficial effects is similar. Because of aspirin's medical antiquity,
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there has been no inclination to explain its actions in terms of an
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"aspirin receptor," as for valium and the opiates, leaving
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its biochemistry, except for the inadequate idea of COX-inhibition,
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simply unexplained.</p>
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<p>If
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we didn't eat linoleic acid and the other so-called "essential
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fatty acids," we would produce large amounts of the "Mead
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acid," n-9 eicosatrienoic acid, and its derivatives. This acid
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in itself is antiinflammatory, and its derivatives have a variety of
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antistress actions. The universal toxicity of the polyunsaturated fats
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that suppress the Mead fats as they accumulate, and the remarkable vitality
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of the animals that live on a diet deficient in the essential fatty
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acids, indicate that the Mead fats are important factors in the stability
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of our mammalian tissues. This protective lipid system probably interacts
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with cellular proteins, modifying the way they bind water and carbon
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dioxide and ions, affecting their electrons and their chemical reactivity.</p>
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<p>If
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salicylic acid and the structurally similar antiinflammatories, local
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anesthetics, muscle relaxants, expectorants, and antihistamines, act
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as surrogates for the absent Mead acid family, and thereby act as defenses
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against all the toxic effects of the unstable fats, it would explain
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the breadth and apparent coherence of their usefulness. And at
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the same time it explains some of the ways that estrogen goes out of
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control, when it exacerbates the toxicity of the accumulated unstable
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fats.</p>
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<p>The
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competition between aspirin and salicylic acid, and other antiinflammatories,
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for the active site on the COX enzyme (Rao, et al., 1982), shows that
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the structural features of these molecules are in some ways analogous
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to those of the polyunsaturated fatty acids. Wherever there are phospholipids,
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free fatty acids, fatty acid esters, ethers, etc. (i.e., in mitochondria,
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chromosomes, cytoskeleton, collagen networks--essentially everywhere
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in and around the cell), the regulatory influence of specific fatty acids--or their surrogates--will be
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felt. </p>
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<p>Although
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it would undoubtedly be best to grow up eating foods with relatively
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saturated fats, the use of aspirin preventively and therapeutically
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seems very reasonable under the present circumstances, in which, for
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example, clean and well ripened fruits are not generally available in
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abundance. Preventing blindness, degenerative brain diseases, heart
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and lung diseases, and cancer with aspirin should get as much support
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as the crazy public health recommendations are now getting from government
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and foundations and the medical businesses.</p>
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<p>When
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people with cancer ask for my recommendations, they usually think I'm
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joking when I tell them to use aspirin, and very often they don't take
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it, on the basis of what seems to be a very strong cultural prejudice.
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Several years ago, a woman whose doctors said it would be impossible
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to operate on her extremely painful "inflammatory breast cancer,"
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had overnight complete relief of the pain and swelling from taking a
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few aspirins. The recognized anti-metastatic effect of aspirin, and
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its ability to inhibit the development of new blood vessels that would
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support the tumor's growth, make it an appropriate drug to use for pain
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control, even if it doesn't shrink the tumor. In studies of many kinds
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of tumor, though, it does cause regression, or at least slows tumor
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growth. And it protects against many of the systemic consequences of
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cancer, including wasting (cachexia), immunosuppression, and strokes.</p>
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<p>Opiates
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are the standard medical prescription for pain control in cancer, but
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they are usually prescribed in inadequate quantities, "to prevent
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addiction." Biologically, they are the most inappropriate means
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of pain control, since they increase the release of histamine, which
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synergizes with the tumor-derived factors to suppress immunity and stimulate
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tumor growth.</p>
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<p>It
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has recently become standard practice in most places to advise a person
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who is having a heart attack to immediately chew and swallow an aspirin
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tablet.</p>
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<p>The
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same better-late-than-never philosophy can be applied to Alzheimer's
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disease, Parkinson's disease, and other degenerative nerve diseases.
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Aspirin protects against several kinds of toxicity, including excitotoxicity
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(glutamate), dopamine toxicity, and oxidative free radical toxicity.
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Since its effects on the mitochondria are similar to those of thyroid
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(T3), using both of them might improve brain energy production more
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than just thyroid. (By activating T3, aspirin can sometimes increase
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the temperature and pulse rate.) Magnesium, niacinamide, and other nerve
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protective substances work together. </p>
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<p>In
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multiple organ failure, which can be caused by profound shock caused
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by trauma, infection, or other stress, aspirin is often helpful, but
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carbon dioxide and hypertonic glucose and sodium are more important. </p>
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<p>Aspirin,
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like progesterone or vitamin E, can improve fertility, by suppressing
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a prostaglandin, and improving uterine circulation.</p>
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<p>Although
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the animal studies that showed stomach damage from aspirin often used
|
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single doses equivalent to 10 or 100 aspirin tablets, the slight irritation
|
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produced by a normal dose of aspirin can be minimized by dissolving
|
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the aspirin in water. The stomach develops a tolerance for aspirin over
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a period of a few days, allowing the dose to be increased if necessary.
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And both aspirin and salicylic acid can be absorbed through the skin,
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so rheumatic problems have been treated by adding the drug to bath water.</p>
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<p>The
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unsaturated (n-6 and n-3) fats that accumulate in our tissues, instead
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of being part of the system for reestablishing order and stability,
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tend to amplify the instability that is triggered by excitation, by
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estrogen, or by external stresses. </p>
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<p>I
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think it's important that we don't allow the drug publicists to obscure
|
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the broad importance of substances such as aspirin, vitamin E, progesterone,
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and thyroid. For 60 years, a myth that was created to sell estrogen
|
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has harmed both science and the health of many people.</p>
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<h2>References</h2>
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<small>
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<p>Free
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Radic Biol Med 2000 Dec 1;29(11):1135-42. <strong>Synergistic inhibition
|
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of cyclooxygenase-2</strong><strong>
|
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expression by vitamin E and aspirin.</strong> Abate A, Yang G, Dennery PA,
|
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Oberle S, Schroder H</p>
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<p>Proc
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Natl Acad Sci U S A 1995 Aug 15;92(17):7926-30. <strong>The mode of action
|
|
of aspirin-like drugs: effect on inducible nitric oxide
|
|
synthase.</strong> Amin AR, Vyas P, Attur M, Leszczynska-Piziak J, Patel
|
|
IR, Weissmann G, Abramson SB. "These studies indicate that the
|
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inhibition of iNOS expression and function represents another mechanism
|
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of action for aspirin, if not for all aspirin-like drugs."</p>
|
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<p>Obstet
|
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Gynecol 2001 Mar;97(3):423-7. <strong>Aspirin effects on
|
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endometrial cancer cell growth.</strong> Arango HA, Icely S, Roberts WS,
|
|
Cavanagh D, Becker JL</p>
|
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<p>J
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Neurochem 2001 Mar;76(6):1895-904. <strong>Neuroprotective effects of
|
|
non-steroidal anti-inflammatory drugs by direct scavenging of nitric
|
|
oxide radicals.</strong> Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno
|
|
M, Ogawa N.</p>
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<p>J
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Neurochem 1998 Oct;71(4):1635-42. <strong>Aspirin and
|
|
salicylate protect against MPTP-induced dopamine depletion in mice.</strong>
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Aubin N, Curet O, Deffois A, Carter C.</p>
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<p>Psychopharmacology
|
|
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acid on cognitive processing: an event-related potentials study.</strong>
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Austermann M, Grotemeyer KH, Evers S, Rodding D, Husstedt IW</p>
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<p>Brain
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Res 1999 Oct 2; 843(1-2): 118-29. <strong>Cyclooxygenase-2 selective inhibitors
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aggravate kainic</strong> <strong>acid induced seizure and neuronal cell death
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<p>Cancer
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Lett 1978 Jun;4(6):333-42. <strong>Inflammatory, tumor initiating and
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promoting activities of polycyclic aromatic hydrocarbons and
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diterpene esters in mouse skin as compared with their
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R, Hecker E.</p>
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<p>J
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Neurooncol 2000;46(3):215-29. <strong>Acetaminophen selectively reduces
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glioma cell growth and increases radiosensitivity in culture.</strong> Casper
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D, Lekhraj R, Yaparpalvi US, Pidel A, Jaggernauth WA, Werner P, Tribius S, Rowe JD, LaSala PA "Glioblastoma
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multiforme (GBM) is a highly lethal brain cancer. Using cultures of
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rodent and human malignant glioma cell lines, we demonstrated that millimolar
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concentrations of acetylsalicylate, acetaminophen, and ibuprofen all
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significantly reduce cell numbers after several days of culture."</p>
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<p>Neurosci
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Lett 2000 Aug 11;289(3):201-4. <strong>Ibuprofen protects
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dopaminergic neurons against glutamate toxicity in vitro.</strong> Casper
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D, Yaparpalvi U, Rempel N, Werner P. "We examined the effects of
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aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic
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neurons from mesencephalon, the area primarily affected in Parkinson's
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disease. We evaluated whether these drugs protect dopaminergic neurons
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against excitotoxicity. All three NSAIDs significantly attenuated the
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decrease in dopamine uptake caused by glutamate, indicating preservation
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of neuronal integrity." </p>
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<p>Lipids
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1996 Aug;31(8):829-37.<strong> Effect of dietary n-9
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eicosatrienoic acid on the fatty acid composition of plasma lipid fractions
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and tissue phospholipids.</strong> Cleland LG, Neumann MA, Gibson RA, Hamazaki T, Akimoto K, James MJ "Dietary
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enrichment with ETrA warrants further investigation for possible beneficial
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effects in models of inflammation and autoimmunity, as well as in other
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conditions in which mediators derived from n-6 fatty acids can affect
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homeostasis adversely."</p>
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<p>Can
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J Ophthalmol 1981 Jul;16(3):113-8.<strong> Senile cataracts: evidence for
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acceleration by diabetes and deceleration by
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salicylate.</strong> Cotlier E.</p>
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<p>Int
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Ophthalmol 1981 May;3(3):173-7. <strong>Aspirin effect on cataract formation
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in patients with rheumatoid arthritis alone or combined with diabetes.</strong>
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Cotlier E. "The effects of aspirin on cataract formation may result
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|
from 1) lowering of plasma tryptophan levels and increased excretion
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|
of tryptophan metabolites, 2) inhibition of aldose reductase and sorbitol
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|
formation in the diabetic lens, 3) inhibition of tryptophan or kynurenine
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binding to lens protein."</p>
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<p>Arterioscler
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Thromb Vasc Biol 2001 Feb;21(2):255-61. <strong>Tamoxifen and cardiac
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risk factors</strong> <strong>in healthy women: Suggestion of an anti-inflammatory
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<p>Med
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Sci Sports Exerc 2001 Dec;33(12):2029-35. <strong>Acetylsalicylic acid
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inhibits the pituitary response to exercise-related stress in humans.</strong>
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Di Luigi L, Guidetti L, Romanelli F, Baldari C, Conte D.</p>
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<p>Ann
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Med 2000 Dec;32 Suppl 1:21-6<strong>. Cyclo-oxygenase products and
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atherothrombosis.</strong> FitzGerald GA, Austin S, Egan K, Cheng Y, Pratico
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D</p>
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<p>Acta
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Diabetol Lat 1981;18(1):27-36. <strong>Effects of acetylsalicylic acid
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on plasma glucose, free fatty acid,
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betahydroxybutyrate, glucagon and C-peptide responses to
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salbutamol in insulin-dependent diabetic subjects.</strong>
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Giugliano D, Passariello N, Torella R, Cerciello T, Varricchio M, Sgambato
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S.</p>
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<p>J
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Reprod Fertil 1994 Aug;101(3):523-9. <strong>Relationships among
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GnRH, substance P, prostaglandins, sex steroids and
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aromatase activity in the brain of the male lizard
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Podarcis sicula sicula during reproduction.</strong> Gobbetti A, Zerani M,
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Di Fiore MM, Botte V "Acetylsalicylic acid decreased PGF2 alpha,
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oestradiol and aromatase activity, but increased the amount of androgens
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released."</p>
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<p>Natl
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Med J India 1998 Jan-Feb;11(1):14-7. <strong>Aspirin: a
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neuroprotective agent at high doses?</strong> Gomes I.</p>
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<p>Radiat Res 1991 Sep;127(3):317-24<strong>.
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Effects of some nonsteroidal anti-inflammatory agents on experimental
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radiation pneumonitis.</strong> Gross NJ, Holloway NO, Narine KR.</p>
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<p>Micron
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2001 Apr;32(3):307-15. <strong>Collagen as a model system to investigate
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the use of aspirin as an inhibitor of protein
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glycation and crosslinking.</strong> Hadley J, Malik N, Meek K.</p>
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<p>J
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Pharmacol Exp Ther 1981 Aug;218(2):464-9. <strong>Protective effects
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of aspirin in endotoxic shock.</strong> Halushka PV, Wise WC, Cook JA.</p>
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<p>J
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Pharmacol Exp Ther 2000 May; 293(2):417-25. <strong>Cyclooxygenase-2 contributes
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to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical
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cell culture.</strong> Hewett SJ, Uliasz TF,
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Vidwans AS, Hewett JA</p>
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<p>Med
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Hypotheses 1999 Apr;52(4):291-2. <strong>Genetic induction and
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upregulation of cyclooxygenase (COX) and
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aromatase (CYP19): an extension of the dietary fat hypothesis of breast
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cancer.</strong> Harris RE, Robertson FM, Abou-Issa HM, Farrar WB, Brueggemeier
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R A novel model of mammary carcinogenesis is proposed involving sequential
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induction and upregulation of cyclooxygenase and aromatase genes by
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essential fatty acids prominent in the US diet.</p>
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<p>J
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Clin Endocrinol Metab 2001 Sep; 86(9):4216-22. <strong>Differential
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effects of E and droloxifene on C-reactive protein and other markers
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of inflammation in healthy postmenopausal women.</strong> Herrington DM, Brosnihan KB, Pusser BE, Seely EW,
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Ridker PM, Rifai N, MacLean DB. "E treatment resulted in 65.8%
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higher levels of C-reactive protein (P = 0.0002) and 48.1% higher levels
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of IL-6...." "These data provide additional evidence of a
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proinflammatory effect of E that may have adverse cardiovascular consequences." </p>
|
|
<p>J
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Natl Cancer Inst 1998 Mar 18;90(6):455-60. <strong>Expression of
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cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer.</strong> Hwang
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D, Scollard D, Byrne J, Levine E "Our results suggest that overexpression
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of COX may not be unique to colon cancer and may be a feature common
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to other epithelial tumors."</p>
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<p>Ginekol
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Pol 1999 Mar;70(3):126-34. <strong>[Evaluation of the effectiveness of a
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low-dose aspirin in the treatment of intrauterine growth retardation
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(IUGR)].</strong> Kalinka J, Sieroszewski P, Hanke W, Laudanski T, Suzin
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J</p>
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<p>J
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Cardiovasc Pharmacol 1995 Feb;25(2):273-81. <strong>Inhibitory effects
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of aspirin on coronary hyperreactivity to
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autacoids after arterial balloon injury in miniature pigs.</strong> Kuga
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T, Ohara Y, Shimokawa H, Ibayashi S, Tomoike H, Takeshita A. "Coronary
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vasoconstriction induced by histamine and serotonin were examined angiographically
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|
before, 1 h, 1 week, and 1 month after balloon injury in 29 hypercholesterolemic
|
|
miniature pigs." "Hyperconstriction induced by the autacoids
|
|
1 h after injury were significantly less in groups B and C than in group
|
|
A (p < 0.01). Hyperconstriction induced by autacoids 1 week after
|
|
injury were significantly less in group B than in group A (p < 0.01)
|
|
and were significantly less in group C than in group A (p < 0.01)
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|
or group B (p < 0.05)."</p>
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|
<p>Proc
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Soc Exp Biol Med 1975 Feb;148(2):329-32. <strong>Correlation of anti-inflammatory
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activity with inhibition of prostaglandin synthesis activity of
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nonsteroidal anti-estrogens and estrogens</strong> (38532). Lerner EJ, Carminati P, Schiatti P.</p>
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<p>Proc
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Soc Exp Biol Med 1985 Feb;178(2):250-3. <strong>Salicylic acid blocks
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indomethacin-induced cyclooxygenase inhibition and lesion formation
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in rat gastric mucosa.</strong> Ligumsky M, Guth PH, Elashoff J, Kauffman
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GL Jr, Hansen D, Paulsen G. "Salicylic acid has been shown to decrease
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gastric mucosal lesions induced by indomethacin in the rat."</p>
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<p>Z
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Naturforsch [C] 2001 May-Jun; 56(5-6):455-63. <strong>Constant expression
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of cyclooxygenase-2 gene in prostate and the lower urinary tract of
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estrogen-treated</strong> <strong>male rats.</strong> Luo C, Strauss L, Ristimaki A,
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Streng T, Santti R.</p>
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<p>Neuropharmacology
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2000 Apr 27;39(7):1309-18. <strong>Mechanisms of the
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neuroprotective effect of aspirin after oxygen and glucose deprivation
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in rat forebrain slices.</strong> Moro MA, De Alba J, Cardenas A, De Cristobal
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J, Leza JC, Lizasoain I, Diaz-Guerra MJ, Bosca L, Lorenzo P "Apart
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|
from its preventive actions against stroke due to its antithrombotic
|
|
properties, recent data in the literature suggest that high concentrations
|
|
of ASA also exert direct neuroprotective effects." "We have
|
|
found that ASA inhibits neuronal damage at concentrations lower than
|
|
those previously reported (0.1-0.5 mM), and that these effects correlate
|
|
with the inhibition of excitatory amino acid release, of NF-kappaB translocation
|
|
to the nucleus and iNOS expression caused by ASA." "Our results
|
|
also show that the effects of ASA are independent of COX inhibition.
|
|
Taken together, our present findings show that ASA is neuroprotective
|
|
in an in vitro model of brain ischaemia at doses close to those recommended
|
|
for its antithrombotic effects."</p>
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|
<p>Pediatrics
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1987 Nov;80(5):638-42. <strong>A catch in the
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Reye.</strong> Orlowski JP, Gillis J, Kilham HA.</p>
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<p>Prostaglandins Leukot Med 1982 Jul;9(1):109-15. <strong>
|
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Effect of acetaminophen and salicylate on aspirin-induced inhibition
|
|
of human platelet cyclo-oxygenase.</strong> Rao GH, Reddy KR, White JG. "Recent
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|
studies have shown that salicylic acid, a metabolite of aspirin, effectively
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|
competes for the same site on the platelet cyclo-oxygenase enzyme."</p>
|
|
<p>Stroke
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|
1997 Oct;28(10):2006-11. <strong>Acetylsalicylic acid increases tolerance
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against hypoxic and chemical hypoxia.</strong> Riepe MW, Kasischke K, Raupach
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A.</p>
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<p>Cancer
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|
Res 1998 Dec 1;58(23):5354-60. <strong>Prevention of
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NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and
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NS-398.</strong> Rioux N, Castonguay A</p>
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<p>J
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Endocrinol 1989 Jun;121(3):513-9. <strong>Indomethacin inhibits the
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effects of oestrogen</strong><strong>
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in the anterior pituitary gland of the rat.</strong> Rosental DG, Machiavelli
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GA, Chernavsky AC, Speziale NS, Burdman JA.</p>
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<p>Int
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|
J Cancer 2001 Aug 15;93(4):497-506.<strong>
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Cyclooxygenase inhibitors retard murine mammary tumor progression by
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reducing tumor cell migration, invasiveness and
|
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angiogenesis.</strong> Rozic JG, Chakraborty C, Lala PK.</p>
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<p>Res
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Commun Mol Pathol Pharmacol 1998 Sep;101(3):259-68. <strong>Protective
|
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ability of acetylsalicylic acid (aspirin) to scavenge radiation induced
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free radicals in J774A.1 macrophage cells.</strong> Saini T, Bagchi M, Bagchi
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D, Jaeger S, Hosoyama S, Stohs SJ.</p>
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<p>Mol Cell Biochem 1999 Sep;199(1-2):93-102. <strong>
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Antioxidant properties of aspirin: characterization of the ability of
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|
aspirin to inhibit silica-induced lipid
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|
peroxidation, DNA damage, NF-kappaB activation, and
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|
TNF-alpha production.</strong> Shi X, Ding M,
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Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V</p>
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<p>J
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Physiol Paris 2001 Jan-Dec;95(1-6):51-7. <strong>Protection by aspirin
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of indomethacin-induced small intestinal damage in rats: mediation by
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salicylic acid.</strong> Takeuchi K, Hase S, Mizoguchi H, Komoike Y, Tanaka
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A. "Most of non-steroidal anti-inflammatory drugs (NSAIDs) except
|
|
aspirin (ASA) produce intestinal damage in rats." "ASA did
|
|
not provoke any damage, despite inhibiting (prostaglandin) PG production,
|
|
and prevented the occurrence of intestinal lesions induced by indomethacin,
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|
in a dose-related manner."</p>
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|
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|
<p>FASEB
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J 2001 Oct;15(12):2057-72. <strong>Cyclooxygenase-independent actions
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of cyclooxygenase</strong><strong>
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inhibitors.</strong> Tegeder I, Pfeilschifter J, Geisslinger G.</p>
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<p>J
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Indian Med Assoc 1997 Feb;95(2):43-4, 47. <strong>Role of low dose aspirin
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in prevention of pregnancy induced hypertension.</strong> Tewari S, Kaushish
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R, Sharma S, Gulati N</p>
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<p>J
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Chromatogr B Biomed Appl 1995 Jul 21;669(2):404-7. <strong>Aspirin
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|
inhibits collagen-induced platelet
|
|
serotonin release, as measured by microbore high-performance liquid
|
|
chromatography with electrochemical detection.</strong> Tsai TH, Tsai WJ,
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|
Chen CF.</p>
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|
<p>Clin
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|
Exp Immunol 1991 Nov;86(2):315-21. <strong>Piroxicam,
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indomethacin</strong><strong> and
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|
aspirin action on a murine fibrosarcoma.</strong> Effects on tumour-associated
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|
and peritoneal macrophages. Valdez JC, Perdigon G. "We also studied
|
|
the effect on tumour development of three inhibitors of prostaglandin
|
|
synthesis: indomethacin, piroxicam and aspirin. Intraperitoneal administration
|
|
of these drugs during 8 d was followed by the regression of palpable
|
|
tumours. Indomethacin (90 mg/d) induced 45% regression, while with piroxicam
|
|
(two 400 mg/d doses and six 200 mg/d doses) and aspirin (1 mg/d) 32%
|
|
and 30% regressions, respectively, were observed. The growth rate of
|
|
nonregressing tumours, which had reached different volumes by the end
|
|
of the treatment, was delayed to a similar extent by the three anti-inflammatory
|
|
non-steroidal drugs (NSAID)."</p>
|
|
<p>Int
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J Radiat Biol 1995 May;67(5):587-96. <strong>Amelioration of radiation
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nephropathy by acetylsalicylic acid.</strong> Verheij M, Stewart FA, Oussoren
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Y, Weening JJ, Dewit L.</p>
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|
<p>Semin
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|
Perinatol 1986 Oct;10(4):334-55. <strong>The role of
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arachidonic acid metabolites in preeclampsia.</strong> Walsh SW, Parisi VM.</p>
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<p>Proc
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Natl Acad Sci U S A 1999 Apr 27;96(9):5292-7. <strong>Suppression of
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inducible cyclooxygenase 2 gene transcription by aspirin and sodium
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salicylate.</strong> Xu XM, Sansores-Garcia L, Chen XM, Matijevic-Aleksic
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N, Du M, Wu KK. "Aspirin and sodium salicylate at therapeutic concentrations
|
|
equipotently blocked COX-2 mRNA and protein levels induced by interleukin-1beta
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|
and phorbol 12-myristate 13-acetate."</p>
|
|
<p>Hum
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|
Reprod 1994 Oct;9(10):1954-7. <strong>The benefits of low-dose aspirin
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|
therapy in women with impaired uterine perfusion during assisted conception.</strong>
|
|
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|
Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR. "Higher pregnancy
|
|
rates (47 versus 17%) were achieved in those taking aspirin from day
|
|
1 of HRT." "The addition of low-dose aspirin to a standard
|
|
HRT protocol in women with impaired uterine perfusion is associated
|
|
with improved blood flow and satisfactory pregnancy rates."</p>
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|
<p>J
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|
Ethnopharmacol 1991 Sep;34(2-3):215-9. <strong>Radiation-protective
|
|
and platelet aggregation inhibitory effects of five traditional Chinese
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|
drugs and acetylsalicylic acid following high-dose gamma-irradiation.</strong>
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Wang HF, Li XD, Chen YM, Yuan LB, Foye WO.</p>
|
|
<p>Fertil
|
|
Steril 1997 Nov;68(5):927-30. <strong>Low-dose aspirin for
|
|
oocyte donation recipients with a thin
|
|
endometrium: prospective, randomized study.</strong> Weckstein LN, Jacobson
|
|
A, Galen D, Hampton K, Hammel J. "Low-dose aspirin therapy improves
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|
implantation rates in oocyte donation recipients with a thin endometrium."</p>
|
|
|
|
<p>Dermatologica
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|
1978;156(2):89-96. <strong>Effect of topical salicylic acid on animal
|
|
epidermopoiesis.</strong> Weirich EG, Longauer JK, Kirkwood AH. In contrast
|
|
to its antihyperplastic effect on pathological proliferation of the
|
|
epidermis, salicylic acid promotes epidermopoiesis in the normal guinea
|
|
pig skin. After the application of 1% w/w salicylic acid in acetone-ethanol
|
|
for 4 weeks, the thickness of the surface epithelium was increased by
|
|
40% and that of the deep epithelium by 19%. The mitotic index rose by
|
|
17%.</p>
|
|
<p>Arch
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|
Exp Veterinarmed 1981;35(3):465-70. <strong>[Control of implantation
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|
in rats and sows by peroral administration of prostaglandin
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|
synthetase inhibitors. 2. Effects of prostaglandin F2 alpha,
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|
progesterone/estrone, and acetylsalicylic acid on implantation and various
|
|
biochemical parameters of amniotic fluid in the rat]</strong> Wollenhaupt
|
|
K, Steger H. "The highest number of normally developed (97 per
|
|
cent) and the lowest number of degenerated foetuses (three per cent)
|
|
were recorded following acetylsalicylic acid treatment, as compared
|
|
to the control group (91 and nine per cent)."</p>
|
|
<p>Biomed
|
|
Pharmacother 1999 Aug;53(7):315-8. <strong>Aspirin induced
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|
apoptosis in gastric cancer cells.</strong> Wong BC, Zhu GH, Lam SK</p>
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|
<p>Scand
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|
J Immunol 2000 Oct;52(4):393-400. <strong>Tamoxifen decreases renal
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|
inflammation and alleviates disease severity in
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autoimmune NZB/W F1 mice.</strong> Wu WM, Lin BF, Su YC, Suen JL, Chiang
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|
BL. "It has been documented that sex hormone may play a role in
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|
the pathogenesis of murine lupus."</p>
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|
<p>Science
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|
2001 Aug 31;293(5535):1673-7. <strong>Reversal of obesity- and diet-induced
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|
insulin resistance with salicylates or targeted disruption of
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Ikkbeta.</strong> Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin
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M, Shoelson SE.</p>
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|
<p>
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|
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|
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