Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats

摘要: Triptolide (TP), a major component of TWHF, is widely used to treat rheumatoid arthritis, systemic lupus erythematosus, nephritis and leprosy. However, its clinical use limited by hepatotoxicity. To further elucidate the underlying mechanism hepatotoxic effects, hepatic gene expression profiles were analyzed. TP (1000 300 μg/kg) was orally administered Wistar rats for 14 days. Current study indicated that female more sensitive TP-induced hepatotoxicity than males. Genome-wide microarray analyses identified 3329 differentially expressed genes in liver rats. Analyses these over-represented functions associated with insulin signaling pathway, glucose metabolism, cell cycle, oxidative stress apoptosis, which consistent results significant increase Caspase-3 activity reduction serum glucose, GSH/GSSG ratio, glucose-6-phosphatase phosphoenolpyruvate carboxykinase activities, glycogen. In addition, it observed first time glucocorticoids IGF1 might get involved These data suggest treatment could alter redox status, reduce induce hepatocyte differential metabolism pathway all contribute overall