The antioxidant effect of leflunomide in septic rats

8. SUMMARYThe Antioxidant Effect of Leflunomide in Septic RatsThe aim of the study: Sepsis is the most mortality cause of the intensive care unitsexcept coronary intensive care units. Sepsis is a pathological condition, which is defined asuncontrolled inflammatory response against the host. The process leads to severe sepsis,septic shock and eventually far organ failure from the primary site and patient death.Leflunomide, is a drug which is used in clinically conditions for its immunomodulatory andantiinflamatory effects. In our study, we investigate the effects of leflunomide use on theseptic oxidative stress. For this purpose, we study the effects of this drug on oxidative stressparameters as superokside dismutase (SOD), catalase (CAT), nitric oxide (NO),malonydialdehyde (MDA) and protein carbonyl (PC) levels.Materials and methods: Wistar Albino type 50 rats were randomly divided into fivegroups; control (n=10), sham (n=10), leflunomide (n=10), sepsis (n=10) andsepsis+leflunomide (n=10) groups. Sepsis was performed with cecal ligation and puncturemethod. Leflunomide 2x10 mg/kg/day was administered via gastric catheter in sepsis andsepsis+leflunomide groups eight and sixteen hours before the experiment. At the end of 24hours rats were sacrificed and bowel tissues were extracted. The tissue levels of SOD, CAT,NO, MDA and PC were measured.Results: SOD level of the sepsis group is significantly lower than control, sham andleflunomide groups (p<0.05). But there is no significant change in sepsis+leflunomide group.CAT level is significantly lower than control, sham, leflunomide groups in sepsis group(p<0.05). But there is no significant change in sepsis+leflunomide group. NO level issignificantly higher in sepsis compared to control, sham, leflunomide and sepsis+leflunomidegroups (p<0.05). In sepsis group MDA level is significantly higher compared to control,sham, leflunomide and sepsis+leflunomide groups (p<0.05). PC level is significantly higher insepsis group than control, sham, leflunomide and sepsis+leflunomide groups (p<0.05).Conclusion: Significant limitation of the protein and lipid peroxidation in sepsis byleflunomide showed that it has also antioxidant effect beside its antiinflammatory effect. Thesignificant limitation of the leflunomide on protein and lipid peroxidation, which occurs insepsis, suggested that drug have anti-inflammatory effects with anti-oxidant properties.It is thought that leflunomide can be used in adjunctive sepsis treatment because of limitationeffect on the beginning and spreading of the sepsis.Key words: Sepsis, leflunomide, and oxidative stress.44