Melatonin protects from ischemia/reperfusion-induced renal injury in rats: this effect is not mediated by proinflammatory cytokines.
The pathophysiologic mechanisms leading to acute ischemic renal failure are not completely understood. Melatonin, a compound with well-known antioxidant properties, reduces IR-induced renal injury. The purpose of the present study was to investigate the changes in levels of tumor necrosis factor (TNF)-alpha, IL-beta, and IL-6 in postischemic reperfused renal tissue, and to determine whether the protective effect of melatonin is related the modulation of the production of these inflammatory molecules. Male Wistar albino rats were unilaterally nephrectomized and subjected to 1 hr of renal pedicle occlusion followed by 2 hr or 24 hr of reperfusion. Melatonin (10 mg/kg, i.p.) or vehicle was administrated at 10 min prior to ischemia. After 24 hr of the reperfusion, following decapitation, kidney samples were taken both for histologic examination and for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, total antioxidant capacity (TAC), total oxidative stress (TOS), creatinine, and blood urea nitrogen (BUN). These were measured in serum samples. TNF-alpha, IL-beta, and IL-6 were measured in kidney samples after 2 hr of reperfusion. IR caused a significant increase in renal MDA, MPO, TOS, creatinine, and BUN while decrease TAC without any change in TNF-alpha, IL-beta, and IL-6 levels. Melatonin treatment reduced the biochemical indices without any change in the cytokine levels and ameliorated histopathologic alterations induced by IR. The protective effect of melatonin on IR-induced renal injury is related to its antioxidant properties but not to proinflammatory cytokines.
Kurcer
Zehra
Z
Department of Pharmacology, Faculty of Medicine, Harran University, Sanliurfa, Turkey. zykurcer@yahoo.com
Oguz
Elif
E
Ozbilge
Hatice
H
Baba
Fusun
F
Aksoy
Nurten
N
Celik
Hakim
H
Cakir
Hale
H
Gezen
Mehmet Riza
MR
D000818:Animals; D003401:Creatine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D007668:Kidney / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009584:Nitrogen / Q000097:blood / Q000652:urine; D018384:Oxidative Stress; D010636:Phenols / Q000378:metabolism; D010936:Plant Extracts / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*
D016207:Cytokines; D010636:Phenols; D010936:Plant Extracts; C501911:antioxidant biofactor AOB; D008550:Melatonin; D003401:Creatine; D009584:Nitrogen