Hepatoprotective activities of zinc and sakuraso-saponin against toxic
ity of carbon tetrachloride were investigated in metallothionein (MT)-
deficient mice. Pretreatment of control 129/Sv mice with zinc or sakur
aso-saponin blocked carbon tetrachloride-induced elevation of plasma t
ransaminase activities. Quantitatively equivalent protection against c
arbon tetrachloride-induced hepatic damage was also observed in MT-def
icient mice. Zinc and sakuraso-saponin caused elevation of hepatic MT
levels in control 12/Sv mice, whereas hepatic MT was undetectable in M
T-deficient mice. To examine the possibility that sakuraso-saponin-ind
uced hepatoprotection is mediated by endogenous zinc, the hepatic conc
entration of zinc was analyzed. Hepatic zinc concentration in MT-defic
ient mice was not changed by the treatment of sakuraso-saponin. Inject
ion of sakuraso-saponin caused a decrease of activity of aniline hydro
xylation. The suppression of cytochrome P450 appears to be a mechanism
by which sakuraso-saponin protects mice from the hepatotoxic effects
of carbon tetrachloride. These findings indicate that the hepatoprotec
tive activity of zinc or sakuraso-saponin is not dependent on their MT
-inducing activity. (C) 1997 Elsevier Science Ireland Ltd.