Replenishing glutathione counters ciprofloxacin-induced acute liver failure via possible gene modifying mechanism

Abstract

Background: Acute liver failure (ALF) can be defined as rapid loss of liver functions even in the absence of pre-existing liver disorders. ALF is a medical emergency that necessitates hospitalization and, if not properly treated, a liver transplant may be the only cure. Herein, we studied the potential therapeutic effects of exogenous glutathione on drug-induced ALF. Materials: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (received only intra-peritoneal injection of distilled water), ciprofloxacin-treated group (received intra-peritoneal injection of 800 mg/kg/day ciprofloxacin for 15 consequent days with concomitant intra-peritoneal injection of distilled water), and ciprofloxacin + glutathione-treated group (received intra-peritoneal injection of 800 mg/kg/day ciprofloxacin for 15 consequent days with concomitant intra-peritoneal injection of 200 mg/kg/day glutathione). Measurement of serum ALT, AST, GGT and LDH enzymes activities were performed, and hepatic gene expression of CYP3A, GPx, GSR and Nrf2 mRNA was assessed. Results: Treatment with ciprofloxacin resulted in significant increase in ALT, AST, GGT and LDH enzymes activities when compared to the control group. Ciprofloxacin also induced significant down-regulation of CYP3A, GPx, GSR and Nrf2 mRNA gene expression when compared to the corresponding values in the control group. Glutathione administration significantly normalized ALT, AST, GGT and LDH enzymes activities and up-regulated CYP3A, GPx, GSR and Nrf2 mRNA gene expression. Conclusion: Glutathione could play potential therapeutic roles in the treatment of acute liver failure by preventing oxidative stress-induced disruption of hepatocyes cell membranes and alteration in cytochrome P450 and the antioxidant genes.