Monoammonium glycyrrhizinate protects rifampicin- and isoniazid-induced hepatotoxicity via regulating the expression of transporter Mrp2, Ntcp, and Oatp1a4 in liver

甘草酸单铵通过调节肝脏中转运蛋白 Mrp2、Ntcp 和 Oatp1a4 的表达来预防利福平和异烟肼引起的肝毒性

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作者:Liting Zhou, Yanqing Song, Jing Zhao, Hongyan Qin, Guoqiang Zhang, Yan Zhou, Xin'an Wu

Conclusion

These results indicated that MAG has a protective effects against RIF- and INH-induced hepatotoxicity. The underlying mechanism may have correlation with its effect on regulating the expression of hepatobiliary membrane transporters.

Methods

Male Wistar rats were randomly divided into four groups of 15 rats. Liver injury was induced by co-treatment with RIF (60 mg/kg) and INH (60 mg/kg) by gavage administration; MAG was orally pretreated at the doses of 45 or 90 mg/kg 3 h before RIF and INH. Rats in each group were sacrificed at 7, 14, and 21 d time points after drug administration.

Objective

This study evaluates the dynamic protective effect of MAG on rifampicin (RIF)- and isoniazid (INH)-induced hepatotoxicity in rats. Materials and

Results

Liver function, histopathological analysis, and oxidative stress factors were significantly altered in each group. The expression of Mrp2 was significantly increased 230, 760, and 990% at 7, 14, and 21 time points, respectively, in RIF- and INH-treated rats. Compared with the RIF and INH groups, Mrp2 was reduced and Ntcp was significantly elevated by 180, 140, and 160% in the MAG high-dose group at the three time points, respectively. The immunoreaction intensity of Oatp1a4 was increased 170, 190, and 370% in the MAG low-dose group and 160, 290, and 420% in the MAG high-dose group at the three time points, respectively, compared with the RIF and INH groups.

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