Regulation effect of isoniazid on the expression of hepatobiliary membrane transporters Mrp2, Bsep, P-gp and Ntcp in mouse / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the regulation effect of isoniazid on the hepatobiliary membrane transporters multidrug resistance protein 2 (Mrp2), bile salt export pump (Bsep), P-glycoproteins (P-gp), sodium taurocholate cotransporting plypeptide (Ntcp), and which would lay the foundation for the studies of the mechanism on isoniazid-induced liver injury from the level of transporters. METHODS: Following an oral dose of 30, 60, 120 mg · kg-1 · d-1 for 1, 2 and 3 months in mouse respectively, the biochemical indicator of serum were determined; the liver were removed for hepatic pathology; the protein mass of Bsep, Mrp2, Ntcp and P-gp were analyzed by Western Blotting. RESULTS: After high/middle/low dose isoniazid administration, the expression of Mrp2, Bsep, P-gp and Ntcp were all changed, especially the high/middle dose group. In addition, the biochemical and pathological were significantly lagged behind the expression change of the transporters. CONCLUSION: The hepatotoxicity of isoniazid may be associated with excessive hepatic accumulation of the related exogenous substances that medicated by Mrp2, Bsep, P-gp and Ntcp.