Aspirin 6-oxidation inhibition

Ashidate K, Kawamura M, Mimura D, Tohda Fi, Miyazaki S, Teramoto T, Hirata Y, Yamamoto Y (2005) Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma. Fur J Pharmacol 513 173... 

Impairment of mitochondrial jj-oxidation leads to accumulation of fat, resulting in steatosis. Examples are various tetracycline derivatives, valproic acid (used to treat seizures) and overdoses of aspirin [64—66]. Certain NSAIDs such as ibuprofen, ketoprofen and naproxen also have the ability to inhibit jj-oxidation [67-69]. 

Aspirin does not alter the normal body temperature, which is maintained by a balance between heat production and dissipation. In a fever associated with infection, increased oxidative processes enhance heat production. Aspirin acts by causing cutaneous vasodilation, which prompts perspiration and enhances heat dissipation. This effect is mediated via the hypothalamic nuclei, as proved by the fact that a lesion in the preoptic area suppresses the mechanism through which aspirin exerts its antipyretic effects. The antipyretic effects of aspirin may be due to its inhibition of hypothalamic prostaglandin synthesis. Although aspirin-induced diaphoresis contributes to its antipyretic effects, it is not an absolutely necessary process, because antipyresis takes place in the presence of atropine. 

This hemostatic/prothrombotic process is counterbalanced by vascular prostacyclin (PGl2) derived predominantly from COX-2 activity and nitric oxide (NO) released from endothelial cells. In vascular endothelial cells, COX-2 produces primarily PGI2 that inhibits platelet aggregation, induces vasodilation, inhibits the proliferation of vascular smooth-muscle cells, and is less susceptible to inhibition by low doses of aspirin. PGI2 and NO induce an intracellular increase of second messengers. NO inhibits platelet function by stimulation of a soluble guanylyl cyclase to produce cGMR... 

Prostaglandins are derived from arachidonic acid, a 20-carbon fatty acid with four cis double bonds. Figure 25-11 shows schematically how an enzyme oxidizes and cyclizes arachidonic acid to give the prostaglandin skeleton. One of the functions of aspirin is to inhibit this enzymatic prostaglandin synthesis and alleviate the inflammatory response. 

There are several drugs that inhibit beta oxidation of fatty acids in mitochondria leading to lipid accumulation, such as aspirin, valproic acid, and tetracyclines. 

The rate of chemical processes affects many facets of our lives. Aspirin is an effective antiinflammatory agent because it rapidly inhibits the synthesis of prostaglandins (Section 19.6). Butter turns rancid with time because its lipids are only slowly oxidized by oxygen in the air to undesirable by-products (Section 15.11). DDT (Section 7.4) is a persistent environmental pollutant because it does not react appreciably with water, oxygen, or any other chemical with which it comes into contact. All of these processes occur at different rates, resulting in beneficial or harmful effects. 

Risk and protective factors of atherosclerosis influence VCAM-1 expression [10,19]. A possible relation between VC AM expression and oxidized LDL was established when an important component of this modified lipoprotein, lysophosphatidylcholine, was shown to stimulate VCAM expression and increase adhesion of monocytes on endothelium in cell cultures [10,18,19]. Modified LDL and its constituents augment c)4 okine-activated VCAM-1 expression in human vascular endothelial cells [10,20]. In contrast, HDL inhibits cytokine-induced expression of endothelial cell adhesion molecules [10,21]. -3 Fatty acids have been found to decrease mRNA levels and surface expression of VCAM-1 in endothelial cells [10,22]. Aspirin inhibits induction of mRNA and cell surface expression of VCAM-1 by TNF-a and thereby inhibits monocyte adhesion on stimulated endothelial cells [10,23]. In contrast to ICAM-1, E-selectin, and P-selectin, endothelial VCAM-1 can mediate leukocyte adhesion via its sole interaction with the integrins 4P1 or 4P7 [10]. 

Aspirin or acetylsalicylic acid, an ester of acetic acid, is the oldest known NSAID and the prototype of the salicylate drugs (Collier 1971, Rogstad Yndestad 1981). In addition to inhibition of COX, salicylates inhibit the formation and release of kinins, stabilize lysosomes and uncouple oxidative phosphorylation (Boothe 1995). In horses, the half-life of aspirin is very short. For example, in ponies, the elimination half-life of aspirin administered i.v. at a dose rate of 19 mg/kg was determined to be approximately 7min (Lees et al 1987a). 

A. Arachidonic acid is produced from linoleic acid (an essential fatty acid) by a series of elongation and desaturation reactions. Arachidonic acid is stored in membrane phospholipids, released, and oxidized by a cyclooxygenase (which is inhibited by aspirin) in the first step in the synthesis of prostaglandins, prostacyclins, and thromboxanes. Leukotrienes require a lipoxygenase, rather than a cyclooxygenase, for their synthesis from arachidonic acid. 

E. Arachidonic acid is cleaved from membrane phospholipids by phospholipase A2, which is inhibited by glucocorticoids. It requires essential fatty acids for its synthesis. It can be converted to leukotrienes, or be oxidized by a cyclooxygenase, which is inhibited by aspirin, and converted to prostaglandins and thromboxanes. 

Fiorucci S, Antonelli E, Santucci L, Morelli O, Miglietti M, et al. 1999. Gastrointestinal safety of nitric oxide-derived aspirin is related to inhibition if ICE-like cysteine proteases in rats. Gastroenterology 116 1089-106... 

Salicylate (aspirin), which also uncouples oxidative phosphorylation in mitochondrial preparations (although at much higher concentrations than 2,4-DNP) (Brody 1956), partially inhibited a protein thiol loss induced by 2,4-DNP, but not nonprotein thiol loss by 2,4-DNP in the small intestine of rats (Nishihata et al. 1988b). Although DNP inhibits the absorption of the hydrophilic drug, cefmetazole, incubation of DNP and salicylate removed this inhibitory effect in the small intestine. By preventing... 

The symptoms of acute gout respond to anli-innammatory drugs suchasindomelh-acin. but it should be noted that these drugs have no direct effect on the serum urate level. Low-dose aspirin should be avoided as it inhibits renal urate excretion. Treatment must also be directed at the hyperuricaemia. Drugs such as probenecid which promote urate excretion can be used prophylactically. A diet which is low in purines and alcohol may be prescribed in an effort to reduce the plasma urate concentration. Allopurinol, a specific inhibitor of the enzyme xanthine oxidase which catalyzes the oxidation... 

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