Measurement of in vivo lipid peroxidation and toxicological significance.

The quantitative determination of hydrocarbons exhaled by animals as an in vivo index of extensive lipid peroxidation is described. Advantages and limitations of this method are discussed. Acetaminophen-induced hepatic lipid peroxidation in mice is an example of oxidative stress, the extent of which is determined in vivo by the turnover of endoplasmic reticulum monooxygenase and the cofactor, e.g. glutathione status of the liver. In microsomal suspensions, none of the assay methods for lipid peroxidation identifies acetaminophen as a prooxidant. Rather, it acts like an antioxidant. The obvious limitations of in vitro experiments are emphasized. Cytosolic metabolism of allyl alcohol also leads, in a dose-dependent manner, to extensive lipid peroxidation. Evidence is presented that release of iron from intracellular stores following overproduction of NADH may be the primary cause of this lesion. The term reductive stress is suggested for this metabolic initiation of iron redox cycling. In experimental hepatitis induced by galactosamine/endotoxin, a leukotriene-mediated pathomechanism, no signs of lipid peroxidation are detectable. This means that ethane or pentane formation are definitively not late consequences of membrane deterioration but rather early causal events in special cases of hepatotoxicity.