Inhibition of lipid peroxidation improves survival rate of endotoxemic rats.
The accumulation of lipoperoxide (LPO) is reported to occur in the organs of animals with endotoxemia, where it is accompanied by an activation of xanthine oxidase (XOD) and a depletion of superoxide dismutase (SOD). In the present study, three measures of preventing LPO accumulation, ie, prior treatment with a XOD inhibitor, exogenous supply of enzymatic scavengers, and supplementation with chemical quenchers, were investigated to determine how to improve the survival rate of rats with lethal endotoxemia. Thirty minutes after treatment with various doses of allopurinol, SOD, catalase (CAT), vitamin E (VE), and reduced glutathione (GSH), adult male Wistar rats were subjected to endotoxemia by an intraperitoneal injection of 0.4 mg/100 g of Escherichia coli endotoxin. Allopurinol did not improve survival rates, denoting a lower level of XOD and an almost normal level of SOD in the liver. SOD (9,000 U/100 g) with or without CAT (4,000 U/100 g) markedly increased the survival rate of rats, with complete inhibition of hepatic LPO accumulation and suppression of XOD activity. CAT alone had no salutary effects on survival rate or hepatic LPO. Large amounts of VE (100 mg/100 g) or GSH (50 mg/100 g) slightly suppressed the accumulation of LPO in the liver but had no effect on survival rate. In that exogenous SOD has been considered not to penetrate the cellular membrane because of its high molecular weight, the results suggest that the extracellular spaces are the site of SOD action. Lipid peroxidation of the biomembrane initiated by oxygen free radicals released into extra-cellular space from phagocytes may play an important role in the development of lethality in experimental endotoxemia.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D004731:Endotoxins; D008054:Lipid Peroxides; D013481:Superoxides; D014810:Vitamin E; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005978:Glutathione