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Heidari R, Esmailie N, Azarpira N, et al. Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver. Toxicol Res. 2016;32(2):133-40doi: 10.5487/TR.2016.32.2.133.
Heidari, R., Esmailie, N., Azarpira, N., Najibi, A., & Niknahad, H. (2016). Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver. Toxicological research, 32(2), 133-40. https://doi.org/10.5487/TR.2016.32.2.133
Heidari, Reza, et al. "Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver." Toxicological research vol. 32,2 (2016): 133-40. doi: https://doi.org/10.5487/TR.2016.32.2.133
Heidari R, Esmailie N, Azarpira N, Najibi A, Niknahad H. Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver. Toxicol Res. 2016 Apr;32(2):133-40. doi: 10.5487/TR.2016.32.2.133. Epub 2016 Apr 30. PMID: 27123164; PMCID: PMC4843982.
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Toxicol Res. 2016 Apr;32(2):133-40. doi: 10.5487/TR.2016.32.2.133. Epub 2016 Apr 30.

Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver.

Toxicological research

Reza Heidari, Neda Esmailie, Negar Azarpira, Asma Najibi, Hossein Niknahad

Affiliations

  1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
  3. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  4. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

PMID: 27123164 PMCID: PMC4843982 DOI: 10.5487/TR.2016.32.2.133

Abstract

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC (500 μM), DTT (400 μM), Vitamin C (200 μM), or vitamin E (200 μM) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

Keywords: Dithioteritol; Drug-induced liver injury (DILI); Glutathione; Hepatoprotection; N-acetyl cysteine; Oxidative stress

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