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Hepatotoxicity of geniposide in rats
T Yamano1, Y Tsujimoto, T Noda
1Osaka City Institute of Public Health and Environmental Science, Japan.
Abstract:
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.
Insights
Geniposide causes liver damage in rats by converting to genipin, which depletes protective liver sulfhydryls. This process can be modulated by cysteine and other agents, offering insights into geniposide hepatotoxicity.
Area of Science:
- Pharmacology
- Hepatology
- Toxicology
Background:
- Geniposide, a compound found in Gardenia jasminoides, has demonstrated potential therapeutic benefits but also raises concerns regarding liver toxicity.
- Understanding the mechanisms underlying geniposide-induced hepatotoxicity is crucial for its safe clinical application.
Purpose of the Study:
- To investigate the hepatotoxic effects of geniposide in a rat model.
- To elucidate the role of genipin, the aglycone of geniposide, and hepatic non-protein sulfhydryls in mediating this toxicity.
Main Methods:
- Oral and intraperitoneal administration of geniposide and genipin to rats.
- Measurement of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.
- Assessment of hepatic non-protein sulfhydryl content.
- In vitro reactivity studies of genipin with sulfhydryl compounds.
- Pretreatment experiments with chloramphenicol, buthionine sulfoximine, and cysteine.
Main Results:
- Oral geniposide administration increased ALT and AST levels, indicating liver damage.
- Hepatotoxicity was reduced by intraperitoneal administration of geniposide or chloramphenicol pretreatment.
- Hepatic non-protein sulfhydryl content decreased dose-dependently after geniposide administration.
- Genipin exhibited reactivity with sulfhydryl groups in vitro.
- Intraperitoneal genipin administration showed comparable toxicity to oral geniposide.
- Buthionine sulfoximine enhanced geniposide toxicity, while cysteine pretreatment abolished it.
Conclusions:
- The conversion of geniposide to genipin is a key factor in its hepatotoxicity.
- Hepatic non-protein sulfhydryls play a significant role in mitigating geniposide-induced liver injury.
- These findings highlight the importance of the genipin metabolite and sulfhydryl status in geniposide toxicity.