Melatonin protected against kidney impairment induced by 5-fluorouracil in mice

The utility of 5-fluorouracil (5-FU) as a successful chemotherapeutic drug for several cancers is limited by the induction of kidney injury and dysfunction due to redox imbalance, inflammation, and apoptosis. Meanwhile, melatonin (MLT) is a potent antioxidant and anti-inflammatory natural compound with a wide safety range. The current study aimed to investigate MLT's protective effect against 5-FU-induced kidney impairment. Male mice were given multiple doses of 5-FU at 25 and 100 mg/kg, as well as MLT at 20 mg/kg. MLT treatment alleviated the toxic effect of 5-FU by normalizing blood urea and creatinine levels and preserving the histological structure, indicating MLT's nephroprotective ability. This is accompanied by body weight maintenance, an increase in survival percentage, and preserved hematological parameters in comparison to the 5-FU-treated mice. MLT's renoprotective effect was explained by improvements in C-reactive protein, IL-6, and caspase-3 in kidney tissue, indicating MLT's anti-inflammatory and antiapoptotic ability. Furthermore, MLT inhibited 5-FU-induced lipid peroxidation by maintaining the activity of superoxide dismutase and catalase, as well as glutathione levels in kidney tissue from mice treated with both doses of 5-FU. The current findings show that MLT has a novel protective effect against 5-FU-induced renal injury and renal impairment.