Hepatotoxicity of geniposide in rats.
The hepatotoxic effects of geniposide were investigated in rats. Increases in serum alanine aminotransferase and aspartate aminotransferase activities as a result of oral administration of 320 mg geniposide/kg body weight were suppressed when geniposide was administered ip or when the rats were pretreated with chloramphenicol. The non-protein sulphydryl content of the liver 4 hr after oral administration of geniposide decrease in a dose-dependent manner. Genipin, the aglycone of geniposide, had a marked reactivity with sulphydryl groups of glutathione and cysteine in vitro. The hepatotoxic effects of ip administration of genipin at a dose of 80 mg/kg body weight were comparable with those of oral administration of geniposide at a dose of 320 mg/kg. Buthionine sulphoximine pretreatment enhanced the toxicity of geniposide, while cysteine pretreatment completely suppressed it. These results suggest that the conversion of geniposide to genipin is causally related to the hepatotoxicity of geniposide and that hepatic non-protein sulphydryls are important in modulating the toxicity.
Osaka City Institute of Public Health and Environmental Science, Japan.
T
T
Yamano
Y
Y
Tsujimoto
T
T
Noda
M
M
Shimizu
M
M
Ohmori
S
S
Morita
A
A
Yamada
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D019328:Buthionine Sulfoximine; D002701:Chloramphenicol / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D057889:Iridoid Glycosides; D039823:Iridoids; D008099:Liver / Q000187:drug effects*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D015394:Molecular Structure; D011714:Pyrans / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism
D057889:Iridoid Glycosides; D039823:Iridoids; D011714:Pyrans; D013438:Sulfhydryl Compounds; C007835:geniposide; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D002701:Chloramphenicol; C007834:genipin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003545:Cysteine; D001663:Bilirubin