The Potential Ameliorative Effects of Melatonin and Tangeretin Against Ischemia/Reperfusion-Induced Acute Renal Injury in Male Rats

Objective: This study aimed to assess whether melatonin and tangeretin individually offer protective effects to the kidneys in a rat model subjected to renal ischemia-reperfusion injury, focusing particularly on their antioxidant, anti-inflammatory and anti-apoptotic effects. Methods: Thirty adult male rats were randomly divided into five groups (n=6): Sham, Ischemia, Vehicle (DMSO), Melatonin and tangeretin. We induced bilateral renal ischemia for 30 min, followed by 2 h of reperfusion. Melatonin at a dose of 10 mg/kg, tangeretin at a dose 20 mg/kg, or the vehicle was administered intraperitoneally 1 h before ischemia. After reperfusion, serum and kidney tissues were collected to analyze markers of renal function, urea and creatinine, along with indicators of kidney damage (KIM-1), inflammation (TNF-α), apoptosis (caspase-3), oxidative stress marker (F₂-isoprostane) and a nuclear protein (HMGB1). Results: The ischemia and vehicle groups showed significantly higher levels of serum creatinine, urea, and increased levels of KIM-1, TNF-α, caspase-3, F₂-isoprostane and HMGB1 in kidney tissues, compared to the sham group (all p<0.05). Treatment with melatonin and tangeretin resulted in decreased biochemical parameters when compared to the ischemia and vehicle groups (all p<0.05), reflecting the protective effect of each agent independently. Conclusion: Melatonin and tangeretin demonstrate substantial protective effects against renal ischemia-reperfusion injury in rats, evidenced by improvements in biochemical markers and decreased tissue damage. This suggests that melatonin and tangeretin hold potential as therapeutic agents for preventing or ameliorating acute kidney injury.