Pretreatment of male BALB/c mice with beta-ionone potentiates thioacetamide-induced hepatotoxicity.
A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, beta-ionone, subcutaneously at 600 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with beta-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice.
Jeong
T C
TC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon, South Korea. tcjung@pado.krict.re.kr
Gu
H K
HK
Park
J I
JI
Yun
H I
HI
Kim
H C
HC
Ha
C S
CS
Roh
J K
JK
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D045792:Norisoprenoids; D013729:Terpenes / Q000633:toxicity*; D013853:Thioacetamide / Q000633:toxicity*
D002273:Carcinogens; D007527:Isoenzymes; D045792:Norisoprenoids; D013729:Terpenes; D013853:Thioacetamide; D003577:Cytochrome P-450 Enzyme System; C008157:beta-ionone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase