Water lipid peroxidation

Biological membranes Fatty acid composition Insufficient watering Lipid peroxidation Mitochondrial membranes... 

Normally, the cascade from oxygen to water is well controlled by SOD, catalase and endogenous antioxidants such as glutathione, ascorbate and vitamin E. Vitamin E is the most important membrane-bound antioxidant. However, during ischaemia, the local control of ROS is lost, thus reactive free radicals can attack the membranes and lipid peroxidation begins. Endogenous antioxidants can be supplemented. This section describes this supplementation strategy. 

Ascorbic acid (vitamin C) is one of the body s endogenous water-soluble antioxidants. Modifications on the ascorbic acid structure have led to some very interesting compounds, such as a novel series of 3-O-alkyl ascorbic-acid derivatives. They have been found to be inhibitors of lipid peroxidation (Nihro etal., 1991). This antioxidant activity is directly related to the lipophilicity of the alkyl chain, su esting that the lipid chain may anchor the antioxidant portion of the molecule in the membrane. 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

A number of water- and fat-soluble nitrogen compounds, e.g., 2,2 -azo-fe/.v(2-amidinopropane) dihydrochloride (ABAP), 2,2 -azo-te(2,4-dimethylvaleroni-trile) (AMVN), and 2,2 -azo-to(2-cyanopropane) (ABCP), form free radicals during decomposition that in the sample to be investigated initiate lipid peroxidation [16] ... 

In 1988 Bast and Haenen [201] reported that both LA and DHLA did not affect iron-stimulated microsomal lipid peroxidation. However, Scholich et al. [202] found that DHLA inhibited NADPH-stimulated microsomal lipid peroxidation in the presence of iron-ADP complex. Inhibitory effect was observed only in the presence of a-tocopherol, suggesting that some interaction takes place between these two antioxidants. Stimulatory and inhibitory effects of DHLA have also been shown in other transition metal-stimulated lipid peroxidation systems [203,204]. Later on, the ability of DHLA (but not LA) to react with water-soluble and lipid-soluble peroxyl radicals has been proven [205], But it is possible that the double (stimulatory and inhibitory) effect of DHLA on lipid peroxidation originates from subsequent reactions of the DHLA free radical, capable of participating in new initiating processes. 

Wang IC, Tai LA, Lee DD, Kanakamma PP, Shen CK, Lull TY, Cheng CH, Hwang KC (1999) CW) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J. Med. Chem. 42 4614 4620. 

As discussed in Section 2.3.3, the mechanism of chloroform-induced liver toxicity may involve metabolism to the reactive intermediate, phosgene, which binds to lipids and proteins of the endoplasmic reticulum, lipid peroxidation, or depletion of GSH by reactive intermediates. Because liver toxicity has been observed in humans exposed to chloroform levels as low as 2 ppm in the workplace and in several animal species after inhalation and oral exposure, it is possible that liver effects could occur in humans exposed to environmental levels, to levels in drinking water, or to levels found at hazardous waste sites. 

Lipid peroxidase inhibition. Water extract of the fresh root, administered intragastrically to infant mice at a dose of 50 mL/kg, was active. The treatment was administered for 7 successive days followed by a single dose of 20% v/v CCI4 in olive subcutaneously at 1 mL/kg on the last day, 1 hour after the administration of the carrot extract . Lipid peroxide formation inhibition. Fresh fruit juice, taken orally by human... 

Antitoxic effect. Sesame oil, adiministered to male Wistar rats, ameliorated hepatic and renal damage in a dose-dependent manner and increased survival in lipopolysaccha-ride-treated rats. It decreased lipid peroxide concentration in serum but not in liver and kidney. Serum nitrite production was unaffected by sesame oil ingestion, and the activity of xanthine oxidase was reduced in the lipopolysaccharide-challenged rats k Anti-tumor activity. Water extract of the dried seed, administered intragastrically to mice at a dose of 50 mg/animal daily for 5 days, was active on CA-Ehrlich-ascites, 18% increase in life-span. Intraperitoneal administration was active on Dalton s lyphoma and CA-Ehrlich-ascites, 19 and 39% increase in life-span, respectively ". Seed oil, administered to rats intraperito-neally with 1,2,5,6-dibenzanthracene or re-tene, was active on sarcoma ". 

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