The role of acrolein in allyl alcohol-induced lipid peroxidation and liver cell damage in mice.

摘要: Male NMRI mice were fed a sucrose diet for 48 hr in order to reduce the hepatic glutathione content and level off its diurnal variation. After administration of allyl alcohol (AA: 1.1 mmol/kg), (24.3 +/- 7.0 nmol GSH/mg protein) was almost totally lost within first 15 min (less than 0.5 protein). Subsequently, massive lipid peroxidation observed, i.e. animals exhaled 414 186 ethane/kg/hr compared 0.9 0.8 controls, TBA-reactive compounds had increased from 55 16 pmol/mg protein controls 317 163 after 1 hr. Concomitantly, 40-45% loss polyunsaturated fatty acids (arachidonic docosahexaenoic acid) liver lipids observed. About 80% cytosolic dehydrogenase activity about 50% microsomal P450-content destroyed. In vivo-inhibition by pyrazole or induction aldehyde phenobarbital abolished AA-induced damage as well depletion peroxidation, while inhibition cyanamide made subtoxic dose AA (0.60 mmol/kg) highly toxic. These results strongly favour importance acrylic acid formation an additional detoxification pathway. Enhanced levels protected vivo against damaging effects AA. Depletion phorone diethylmaleate alone caused marginally enhanced (phorone) but not cell damage. Monooxygenase inhibitors (metyrapone, diethyldithiocarbamate, alpha-naphthoflavone) inducer (benz(a)pyrene) did affect toxicity. The ferric iron chelator desferoxaminemethanesulfonate prevented vivo. vitro, acrolein failed initiate soy bean phospholipid liposomes mouse microsomes. Thus, only impairs defense system also directly destroys cellular proteins evokes indirect iron-depending mechanism.