Abstract

Lead is a common environmental metal known to cause toxicity to multiple organs, with the kidneys being the primary target of lead poisoning due to their role in lead excretion. Quercetin is a natural flavonoid with reported antioxidant and protective properties. However, despite these properties, its preventive or therapeutic role in lead-induced toxicity has not been fully elucidated. The present study aimed to evaluate the preventive effect of quercetin against lead acetate–induced nephrotoxicity in rats. Twenty adult male rats were randomly divided into four groups: a control group, a lead-treated group administered 241 mg/kg body weight (1/20 LD₅₀) of lead acetate orally, a quercetin-treated group receiving 40 mg/kg body weight of quercetin, and a combined lead plus quercetin group. Renal injury was assessed using biochemical markers of oxidative stress, molecular analysis of metallothionein-2 (MT2) gene expression, and histopathological examination of kidney tissue. The results showed that lead exposure induced significant renal toxicity, evidenced by increased kidney injury molecule-1 (KIM-1) and malondialdehyde (MDA) levels, altered superoxide dismutase (SOD) activity, marked upregulation of MT2 gene expression, and severe histopathological alterations in renal tissue. Co-administration of quercetin significantly attenuated lead-induced oxidative stress, reduced KIM-1 levels, modulated MT2 expression, and alleviated the severity of renal histopathological lesions. However, quercetin did not fully restore biochemical or histological parameters to control levels. Quercetin alone did not induce renal injury and was associated with reduced oxidative stress markers. In conclusion, Lead acetate induces nephrotoxicity by a mechanism mediated by oxidative stress. Quercetin provides partial nephroprotection and may serve as a supportive preventive agent against renal toxicity caused by lead, but does not fully compensate for the renal damage caused by lead.