Role of Lipid Peroxidation as a Mechanism of Liver Injury after Acetaminophen Overdose in Mice

摘要: Mitochondrial oxidant stress and peroxynitrite formation have been implicated in the pathophysiology of acetaminophen-induced (AAP-induced) liver injury. Therefore, we tested hypothesis that lipid peroxidation (LPO) might be involved injury mechanism. Male C3Heb/FeJ mice fed a diet high vitamin E (1 gd --tocopheryl acetate/kg diet) for 1 week had 6.7-fold higher hepatic tocopherol levels than animals on control (8.2 0.1 nmol/g liver). Treatment fasted with 300 mg/kg AAP caused centrilobular necrosis plasma alanine amino- transferase (ALT) activities at 6 h (3280 570 U/l) but no evi- dence LPO (hepatic malondialdehyde, 4-hydroxynonenal). An- imals similar as diet. To verify potential effect drug-induced injury, were pretreated combination phorone, FeSO4, allyl alcohol. We observed, 2 after alcohol, massive cell livers diet, indicated by 32-fold increase malondialdehyde levels, extensive staining 4-hy- droxynonenal, ALT 2310 340 U/l. Animals 40% lower 85% values. Similar results obtained when treated 3 days -o r-tocopherol (0.19 mmol/kg, ip). Both treatments reduced alcohol hepatotoxicity. Thus, despite previously shown mitochondrial formation, does not appear to critical event AAP- induced