Metallothionein-independent hepatoprotection by zinc and sakuraso-saponin.
Hepatoprotective activities of zinc and sakuraso-saponin against toxicity of carbon tetrachloride were investigated in metallothionein (MT)-deficient mice. Pretreatment of control 129/Sv mice with zinc or sakuraso-saponin blocked carbon tetrachloride-induced elevation of plasma transaminase activities. Quantitatively equivalent protection against carbon tetrachloride-induced hepatic damage was also observed in MT-deficient mice. Zinc and sakuraso-saponin caused elevation of hepatic MT levels in control 129/Sv mice, whereas hepatic MT was undetectable in MT-deficient mice. To examine the possibility that sakuraso-saponin-induced hepatoprotection is mediated by endogenous zinc, the hepatic concentration of zinc was analyzed. Hepatic zinc concentration in MT-deficient mice was not changed by the treatment of sakuraso-saponin. Injection of sakuraso-saponin caused a decrease of activity of aniline hydroxylation. 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 hepatoprotective activity of zinc or sakuraso-saponin is not dependent on their MT-inducing activity.
Itoh
N
N
Environmental Toxicology, Pharmaceutical Sciences, Osaka University, Suita, Japan.
Kimura
T
T
Nakanishi
H
H
Muto
N
N
Kobayashi
M
M
Kitagawa
I
I
Tanaka
K
K
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008668:Metallothionein / Q000172:deficiency*; D051379:Mice; D008815:Mice, Inbred Strains; D012503:Saponins / Q000494:pharmacology*; D000637:Transaminases / Q000378:metabolism; D015032:Zinc / Q000032:analysis / Q000494:pharmacology*
D012503:Saponins; D003577:Cytochrome P-450 Enzyme System; D008668:Metallothionein; D002251:Carbon Tetrachloride; D000637:Transaminases; D015032:Zinc