Reza Heidari
1, Nazanin Sadeghi
2, Negar Azarpira
3, Hossein Niknahad
1,2*1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
3 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
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.