Prevention of renal ischemia/reperfusion-induced injury in rats by leflunomide.
OBJECTIVE
There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of leflunomide, an isoxazole derivative and a unique immunomodulatory agent, in I/R-induced renal injury in rats.


METHODS
Forty female Sprague-Dawley rats were divided equally into four groups: (I) control (only leflunomide 10 mg/kg, intragastrically treated); (II) sham operated (only unilateral nephrectomy); (III) I/R; and (IV) leflunomide (10 mg/kg for two doses prior to experiment) plus I/R groups. In groups III and IV, after unilateral nephrectomy, the rats were subjected to 60 min of left renal pedicle occlusion, followed by 6 h of reperfusion. At the end of the reperfusion period, rats were killed and kidneys and blood were removed. Catalase, myeloperoxidase and xanthine oxidase activities, and malondialdehyde, nitric oxide and protein carbonyl levels were determined in renal tissue. Serum creatinine, blood urea nitrogen and aspartate aminotransferase were measured for the evaluation of renal function. In histopathological examination, renal damage was scored 0-3.


RESULTS
Group III animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with leflunomide markedly attenuated renal dysfunction, morphological alterations, reduced elevated oxidative stress products levels and restored the depleted renal antioxidant enzyme.


CONCLUSIONS
The findings imply that oxygen radicals play a causal role in I/R-induced renal injury, and leflunomide exerts renoprotective effects probably by the radical scavenging and antioxidant activities with immunomodulatory effect.
Karaman
Abdurrahman
A
Inonu University, Faculty of Medicine, Department of Pediatric Surgery, Malatya, Turkey. akaraman@inonu.edu.tr
Turkmen
Emine
E
Gursul
Cebrail
C
Tas
Erkan
E
Fadillioglu
Ersin
E
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D000077339:Leflunomide; D015227:Lipid Peroxidation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009569:Nitric Oxide; D003404:Creatinine; D002374:Catalase; D009195:Peroxidase; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D000077339:Leflunomide