title: Altered integrity and decreased expression of hepatocyte tight junctions in rifampicin-induced cholestasis in mice.
abstract: 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.
authors: Department of Gastroenterology, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors: Xi
authors: X
authors: Chen
authors: Cheng
authors: C
authors: Zhang
authors: Hua
authors: H
authors: Wang
authors: Juan
authors: J
authors: Xu
authors: Zi-Hao
authors: ZH
authors: Duan
authors: Ying
authors: Y
authors: Zhang
authors: Tao
authors: T
authors: Yu
authors: Wei
authors: W
authors: Wei
authors: De-Xiang
authors: DX
authors: Xu
authors: Jian-Ming
authors: JM
authors: Xu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018613:Microscopy, Confocal; D012293:Rifampin / Q000008:administration & dosage / Q000633:toxicity*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D012293:Rifampin