Impact of combined ischemic preconditioning and melatonin on renal ischemia-reperfusion injury in rats

Objective(s): Studying the effect of melatonin pretreatment and ischemic preconditioning on renal ischemia-reperfusion injury (IRI). Materials and Methods: Forty-eight Wistar rats were randomized into six groups: control, sham operation, IRI (IRI in left kidney + right nephrectomy), IRI+ischemic preconditioning, IRI+Melatonin, and IRI+ischemic preconditioning+Melatonin groups. Melatonin (۱۰ mg/kg) was intraperitoneally injected for ۴ weeks before renal IRI. Ischemic preconditioning was performed by three cycles of ۲ min-ischemia followed by ۵ min-reperfusion period. A right nephrectomy was initially done and the left renal artery was clamped for ۴۵ min. After ۲۴ hr of ischemia-reperfusion, rats were decapitated. Kidney tissue samples were taken for histopathological assessment and the determination of kidney proinflammatory and anti-inflammatory cytokines, apoptotic protein caspase-۳, oxidative stress markers, and activities of antioxidant enzymes. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for evaluation of renal function. Results: Renal IRI animals showed increased levels of creatinine, BUN, tumor necrosis factor-α (TNF-α), caspase-۳, total nitrite/nitrate, and malondialdehyde (MDA), and decreased levels of interleukin-۱۳ (IL-۱۳), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Melatonin pretreatment or ischemic preconditioning resulted in decreased creatinine, BUN, TNF-α, caspase-۳, nitrite/nitrate, and MDA, and increased IL-۱۳, GPx, and SOD, with improved histopathological changes. Combined melatonin and ischemic preconditioning showed more effective improvement in renal IRI changes rather than melatonin or ischemic preconditioning alone. Conclusion: Combined melatonin and ischemic preconditioning have better beneficial effects on renal IRI than applying each one alone. 

Keywords:

Ischemic preconditioning , Ischemia-reperfusion injury , Melatonin , Oxidative stress , Wistar rat