Toxicological Research

  • 제32권2호
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  • Pages.133-140
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  • 2016
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

  • Heidari, Reza (Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences) ;
  • Esmailie, Neda (Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences) ;
  • Azarpira, Negar (Transplant Research Center, Shiraz University of Medical Sciences) ;
  • Najibi, Asma (Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences) ;
  • Niknahad, Hossein (Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences)
  • 투고 : 2015.04.10
  • 심사 : 2015.07.03
  • 발행 : 2016.04.15
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초록

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 ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) 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.

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