SYNERGISTIC ANTIOXIDANT EFFECTS OF MELATONIN AND ZINC AGAINST LEAD-INDUCED RENAL INJURY IN RATS

Abstract

This study investigated the nephroprotective efficacy of combined melatonin and zinc therapy against lead acetate (PbAc)-induced renal toxicity in a rat model. Eighty male Wistar rats were randomized into five experimental groups: negative control, PbAc (50 mg/kg/day), PbAc+melatonin (10 mg/kg/day), PbAc+zinc (20 mg/kg/day), and PbAc+melatonin+zinc, with treatments administered orally for 8 weeks.

Quantitative analysis revealed the combination therapy significantly attenuated PbAc-induced renal dysfunction, reducing serum creatinine by 45.6% (p<0.001) and blood urea nitrogen by 43.4% (p<0.001) compared to PbAc-exposed animals. Oxidative stress parameters demonstrated marked improvement, with malondialdehyde levels decreasing 56.3% (p<0.001), superoxide dismutase activity increasing 112.2% (p<0.001), and glutathione content rising 147.6% (p<0.001). Proinflammatory cytokines TNF-α and IL-6 were reduced by 51.4% and 56.0% respectively (both p<0.001). Histopathological evaluation showed the combination treatment reduced tubular degeneration by 62.8% (p<0.001) and interstitial infiltration by 63.7% (p<0.001) versus PbAc controls.

Mechanistically, the superior protection afforded by combination therapy appears mediated through complementary pathways: zinc’s metal chelation and metallothionein induction coupled with melatonin’s potent free radical scavenging and anti-inflammatory properties. While demonstrating significantly greater efficacy than monotherapies (p<0.01 for all parameters), persistent mild histological alterations suggest incomplete reversal of established damage, potentially reflecting irreversible cellular injury or residual lead burden. These findings provide compelling preclinical evidence for the therapeutic potential of combined antioxidant and chelation strategies in heavy metal nephrotoxicity