[Effect of emodin on P-gp expression in intrahepatic cholestatic rats].

OBJECTIVE

To investigate the effect and mechanism of emodin on acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in rats.

METHOD

Acute cholestatic model in rats was induced by ANIT. Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treatment were set up. Liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transport protein genes mdr1a (multidrug resistance protein 1a), mdr1b (multidrug resistance protein 1b) mdr2 (multidrug resistance protein 2), The expression of P-gp were determined by Western blotting analysis.

RESULT

Compared to the model group, Emodin treatment resulted in significant reductions in serum total bilirubin (TBiL), direct bilirubin (DBiL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA) (P < 0.01 or P < 0.05). By examining the liver pathology, it was found that hepatic cellular change and necrosis, inflammatory cell infiltration and bile duct proliferation were notably alleviated in emodin model with ANIT treatment. Analysis of gene expression in livers from emodin-treated cholestatic rats revealed that mdr1a, mdr1b and mdr2 could be up-regulated (P < 0.01 or P < 0.05), expression of P-gp was increased in accordance with its mRNA (P < 0.05).

CONCLUSION

Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile-metabolism-related transporter P-gp in the liver to prevent bile acids and other toxic compounds overaccumulation in hepatocytes and hepatic toxicity.