Cytotoxic effects of paraquat and inhibition of them by vitamin E.
Paraquat causes failure of multiple organs including the liver in humans. The kinetics and mechanism of paraquat intoxication were studied using cultured rat hepatocytes. Paraquat induced time- and dose-dependent lactate dehydrogenase release, lipid peroxidation, and cell death, estimated as decrease in protein in cells attached to culture dishes. However, the increase in lipid peroxidation occurred after lactate dehydrogenase release had reached a plateau. Vitamin E inhibited the inductions of all these cytotoxic effects of paraquat. Kinetic studies showed that lipid peroxidation was a better indicator of cell death than lactate dehydrogenase release, because vitamin E inhibited the induction of cell death even when added 6 h after paraquat, when lactate dehydrogenase release had reached a plateau but lipid peroxidation had not. The present results strongly suggest that paraquat exerts its cytotoxicity by a mechanism involving oxidation reactions.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D008054:Lipid Peroxides; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D010269:Paraquat