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.