RETINOID X RECEPTOR α PARTICIPATION IN DEXAMETHASONE-INDUCED RAT BILE ACID COENZYME A-AMINO ACID N-ACYLTRANSFERASE EXPRESSION IN SEPTIC LIVER

To test the hypothesis that dexamethasone (Dex) treatment would restore rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT) expression in septic rats after cecal ligation and puncture by increasing expression of retinoic acid X receptor alpha (RXR alpha), we assessed survival rate and bile and bile salt concentration in the Dex-treated septic group and compared these results with those for a nontreated septic group, a Dex-treated nonseptic group, and a sham group. Dexamethasone treatment (0.01 mg/kg) significantly improved the survival rate and increased the bile and bile salt concentration in the bile ducts of septic rats (P = <0.05). In our assessment of bile salt-related genes, during sepsis, there were decreases in protein and mRNA expression of rBAT and cholesterol 7 alpha-hydroxylase (CYP7A1). Treatment with Dex restored expression of rBAT and RXR alpha but not CYP7A1, bile salt export pump, or multicrug resistance associated protein 2 (MRP2). Na+-taurocholate cotransport protein and organic anion transporting polypeptide 1 were unchanged. In addition, treatment with Dex also restored the DNA-binding activity of RXR/farnesoid-X receptor to rBAT promoter containing inverted repeat 1 sequence. In an experiment to confirm our findings, RXR alpha siRNA was found to significantly block Dex-induced increases in expression of rBAT in hepatocytes taken from septic rats (P < 0.01). Conclusion-Dex restored the expression of rBAT in septic rats by enhancing RXR alpha, a process that might explain the mechanism underlying Dex's anticholestatic effect.