Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats.
The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.
Wang
C J
CJ
Department of Biochemistry, Chung-Shan Medical and Dental College, Taichung, Taiwan, Republic of China.
Wang
S W
SW
Lin
J K
JK
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000096:biosynthesis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000096:biosynthesis; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis; D005978:Glutathione / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D039823:Iridoids; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D039823:Iridoids; D011714:Pyrans; C007835:geniposide; D004247:DNA; D016604:Aflatoxin B1; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione