Buthionine sulfoximine inhibition of glutathione biosynthesis enhances hepatic lipid peroxidation in rats during acute ethanol intoxication.
A single intraperitoneal injection of DL-buthionine-S,R-sulfoximine (BSO) (4 mmol/kg) to overnight-starved rats caused a 70% inhibition of hepatic gamma-glutamylcysteine synthetase and induced a decrease in liver-reduced glutathione (GSH) for several hours. There was, however, no difference in hepatic lipid peroxidation, as assessed by malondialdehyde accumulation, between the control and BSO groups. During acute ethanol intoxication (5 g/kg), hepatic lipid peroxidation was increased by approx. 40% within 6 hr. Hepatic [GSH] was also significantly decreased by ethanol. The effect of ethanol on GSH level was not observed in rats pretreated with BSO, though the ethanol-induced enhancement of hepatic lipid peroxidation was potentiated by the BSO pretreatment. Under these conditions there were no apparent effects on blood concentrations of ethanol and acetaldehyde nor on activities of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, glutathione-dependent detoxifying enzymes, superoxide dismutase or catalase. These results suggest that, although a decrease (by BSO) in GSH by itself does not alter the degree of endogenous lipid peroxidation, it is associated with a potentiation of the enhancement of hepatic lipid peroxidation caused by acute ethanol intoxication.
Kera
Y
Y
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan.
Ohbora
Y
Y
Komura
S
S
D000435:Alcoholic Intoxication / Q000201:enzymology*; D000818:Animals; D000963:Antimetabolites; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D000963:Antimetabolites; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D010453:Peptide Synthases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione