Altered integrity and decreased expression of hepatocyte tight junctions in rifampicin-induced cholestasis in mice

作者：Chen, Xi; Zhang, Cheng; Wang, Hua; Xu, Juan; Duan, Zi-Hao; Zhang, Ying; Yu, Tao; Wei, Wei; Xu, De-Xiang; Xu, Jian-Ming^*

来源：Toxicology and Applied Pharmacology, 2009, 240(1): 26-36.

DOI：10.1016/j.taap.2009.06.022

• Cholestasis
• Rifampicin
• Hepatocyte tight junctions
• Zonula occludens
• Occludin

Rifampicin is a well-known hepatotoxicant, but little is known about the mechanism of rifampicin-induced hepatotoxicity. The aim of this study was to characterize the expression and localization of hepatocyte tight junctions in rifampicin-induced cholestasis in mice. Cholestasis was induced by administration of rifampicin (200 mg/kg) for 7 consecutive days or treatment with a single dose of rifampicin (200 mg/kg) by gastric intubation, The expression of mRNA for hepatic zonula occludens (ZO)-1, ZO-2, ZO-3, occludin and claudin-1 was determined using RT-PCR. Localization of ZO-1 and occludin was detected using immunofluorescence. Results showed that there was an 82-fold increase in the conjugated bilirubin in serum in rifampicin-treated mice. In addition, an 8-fold increase in total bile acid in serum was observed after a seven-day administration of rifampicin. The integrity of hepatocyte ZO-1 and occludin was altered by a seven-day administration of rifampicin. importantly, the integrity and intensity of hepatocyte tight junctions were altered as early as 30 min after a single dose of rifampicin. The expression of hepatic ZO-1 and ZO-2 mRNA was significantly decreased, beginning as early as 30 min and remaining a lower level 12 h after a single dose of rifampicin. Taken together, these results suggest that the altered integrity and internalization of hepatocyte tight junctions are associated with rifampicin-induced cholestasis.

• 出版日期2009-10-1
• 单位安徽医科大学