Sulfasalazine-Induced Hepatic Injury in an Ex Vivo Model of Isolated Perfused Rat Liver and the Protective Role of Taurine

摘要

Sulfasalazine is one of the most commonly administered drugs for the treatment of rheumatoid arthritis and inflammatory bowel disease in humans. On the other hand, acute liver failure led to liver transplantation and/or patient death might occur after sulfasalazine administration. There is no precise mechanism for hepatic injury induced by sulfasalazine and no specific hepatoprotective agent has been developed against this complication. Current investigation was designed to study oxidative stress as a proposed mechanism for sulfasalazine-induced liver injury and evaluate the role of taurine administration as a safe hepatoprotective agent. Methods: Rat liver was isolated after cannulation through portal vein and perfused with Krebs-Henseleit buffer. The liver was exposed to different concentrations of sulfasalazine and taurine. Results: Sulfasalazine (5 mM) administration caused significant hepatic injury as judged by elevation in liver perfusate level of LDH, AST, ALT, and potassium ion (K+). Significant amounts of reactive oxygen species (ROS) and lipid peroxidation were detected in sulfasalazine treated livers. Furthermore, hepatic glutathione reservoirs were depleted. Histopathological examination of liver tissues confirmed the above mentioned biochemical data. Co-administration of taurine (5, 10 and 20 mM), significantly mitigated sulfasalazine-induced hepatic injury in isolated rat liver. Conclusion: The data obtained from current investigation indicate potential therapeutic properties of taurine against sulfasalazine-induced liver injury.