Potentiation of carbon tetrachloride hepatotoxicity by piperine.
The effect of piperine on CCl4-induced hepatotoxicity was investigated in rats. Piperine pretreatment potentiated the hepatotoxicity of CCl4 in a dose-dependent manner. The maximum potentiation occurred when piperine at a dose of 100 mg/kg BW was intragastrically administered 4 h prior to an intraperitoneal injection of CCl4, at which time the activities of plasma glutamic pyruvic transaminase (PGPT) and plasma glutamic oxaloacetic transaminase (PGOT) were elevated by 70-80%. Concurrent with the rise in PGPT and PGOT activities, the accumulation of hepatic triglyceride increased whereas the plasma level of triglyceride decreased. Piperine pretreatment also potentiated CCl4-induced lipid peroxidation in the liver. The extent of potentiation correlated well with the rise of hepatic enzyme activity in plasma. In the in vitro system in which the tissue was preincubated with piperine and CCl4 was added into the incubation medium, piperine also exhibited a concentration dependent potentiation on CCl4-induced lipid peroxidation and on the activity of NADPH-cytochrome c-reductase. The results indicated that piperine potentiated CCl4-induced hepatotoxicity by interacting with liver cells and increased the activity of NADPH-cytochrome c reductase. The increase in activity of this enzyme accelerated biotransformation of CCl4, thereby increasing lipid peroxidation and enhancing hepatotoxicity.
Piyachaturawat
P
P
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Kingkaeohoi
S
S
Toskulkao
C
C
D000410:Alanine Transaminase / Q000097:blood; D000470:Alkaloids; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D052117:Benzodioxoles; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000633:toxicity*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D052117:Benzodioxoles; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D002251:Carbon Tetrachloride; D009251:NADPH-Ferrihemoprotein Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C008922:piperine