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 pi perine at a dose of 100 mg/kg BW was intragastrically administered 4 h prior to an intraperitoneal injection of CCl4, at which time the acti vities of plasma glutamic pyruvic transaminase (PGPT) and plasma gluta mic oxaloacetic transaminase (PGOT) were elevated by 70-80%. Concurren t with the rise in PGPT and PGOT activities, the accumulation of hepat ic triglyceride increased whereas the plasma level of triglyceride dec reased. Piperine pretreatment also potentiated CCl4-induced lipid pero xidation 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 d ependent potentiation on CCl4-induced lipid peroxidation and on the ac tivity of NADPH-cytochrome c-reductase. The results indicated that pip erine potentiated CCl4-induced hepatotoxicity by interacting with live r cells and increased the activity of NADPH-cytochrome c reductase. Th e increase in activity of this enzyme accelerated biotransformation of CCl4, thereby increasing lipid peroxidation and enhancing hepatotoxic ity.