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Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver

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Abstract

Hepatic ischemia-reperfusion (I/R) injury may be developed in some conditions, such as trauma, major hepatic resection, hemorrhagic shock or liver transplantation. I/R injury of the liver causes hepatocellular damage that may lead to hepatic failure. A considerable body of evidence indicates that reactive oxygen species (ROS) and inflammation may contribute to hepatocellular injury in liver I/R. Leflunomide is an isoxazole derivative, and a unique immunomodulatory agent. In the present study, we examined the effects of leflunomide on the neutrophil activation with oxidative stress and some antioxidant enzymes in the reperfusion following I/R in the rat liver. Thirty-two rats divided into four groups: group 1 (control); was given leflunomide 10 mg/kg, i.g.; group 2 (SHAM), animals were only laparotomized; group 3 (liver I/R), and group 4 (liver I/R + Leflunomide). In group 4, rats were pretreated with leflunomide (10 mg/kg, i.g.) two doses prior to experiment. In groups 3 and 4, occluding the hepatic pedicel for 60 min induced ischemia and reperfusion was allowed thereafter for 60 min. At the end of the reperfusion period, rats were sacrificed. superoxide dismutase, catalase, nitric oxide, xanthine oxidase, malondialdehyde, protein carbonyl and myeloperoxidase levels were determined in hepatic tissue as well as histological examination with H and E staining. Group 3 animals demonstrated severe deterioration of liver morphology and a significant liver oxidative stress. Pretreatment of animals with leflunomide markedly attenuated morphological alterations and neutrophil activation, reduced elevated oxidative stress products levels and restored the depleted hepatic antioxidant enzyme. The findings imply that ROS play a causal role in I/R-induced hepatic injury, and leflunomide exerts hepatoprotective effects probably by the anti-inflammatory effect with radical scavenging and antioxidant activities.

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Authors and Affiliations

  1. Turgut Özal Medical Centre, Department of Pediatric Surgery, Inönü University School of Medicine, 44280, Malatya, Turkey

    Abdurrahman Karaman & Erkan Tas

  2. Turgut Özal Medical Centre, Department of Physiology, Inönü University School of Medicine, 44280, Malatya, Turkey

    Ersin Fadillioglu & Zumrut Yilmaz

  3. Turgut Özal Medical Centre, Department of Pathology, Inönü University School of Medicine, 44280, Malatya, Turkey

    Emine Turkmen

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  1. Abdurrahman Karaman
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Correspondence to Abdurrahman Karaman.

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Karaman, A., Fadillioglu, E., Turkmen, E. et al. Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver. Ped Surgery Int 22, 428–434 (2006). https://doi.org/10.1007/s00383-006-1668-x

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