Hydroxy radical, lipid peroxidation

Figure 17.2 Lipid peroxidation scheme. LH, a polyunsaturated fatty acid LOOM, lipid hydroperoxide LOH, lipid alcohol L, lipid radical LOO, lipid hydroperoxyl radical LO, lipid alkoxyl radical. Initiation the LH hydrogen is abstracted by reactive oxygen (e.g. lipid alkyl radical, lipid alkoxy radical, lipid hydroperoxyl radical, hydroxy radical, etc.) to produce a new lipid alkyl radical, L. Propagation the lipid alkyl, alkoxyl or hydroperoxyl radical abstracts hydrogen from the neighbouring LH to generate a new L radical.

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Chemiluminescence has been used to investigate lipid peroxidation on the brains of rats. Cerebral hypoxia was induced by arterial hypoxaemia fP p2 17-22 mmHg) with normocapnia (/%°2 28-38 mmHg) and normotension (MABP 100-140 mmHg). Mixed gas (02/N2, 4/96%) was used as a replacement for obtaining lowered E 2. The chemiluminescence findings indicate that vitamin E and betamethasone act on the breakdown of lipid hydroperoxide and that mannitol acts on hydroxy radicals in lipid peroxidation [183-185], A recent study has found that phenytoin is superior to vitamin E as a protectant in a mouse cerebral infarction model [ 186] and that this effect is enhanced by combination with mannitol and vitamin E. 

Hamdane M, Delobel P, Sambo AV, Smet C, Begard S, fioUeau A, Landrieu I, Delacourte A, Lippens G, Flament S, Buee L (2003) Neurofibrillary degeneration of the Alzheimer-type tm alternate pathway to neuronal apoptosis Biochem Pharmacol 66 1619-1625 Hayashi T, Shishido N, Nakayama K, Nunomura A, Smith MA, Perry G, Nakamura M (2007) Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-beta peptide. Free Radic Biol Med 43 1552-1559... 

Reactive oxygen species (ROS), such as superoxide anion and hydroxy radical, induce lipid peroxidation (LPO) which injuries cell membranes. 

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