Nephroprotective effect of vitamin E and sodium selenite against azithromycin-induced renal toxicity in a rat model: attenuation of oxidative stress, inflammation, and apoptosis

Background Azithromycin (AZM), a widely prescribed macrolide antibiotic, has been increasingly associated with nephrotoxicity mediated by oxidative stress, inflammation, and apoptosis. Antioxidants such as vitamin E and sodium selenite may exert protective effects against drug-induced nephrotoxicity.Objectives This study aimed to investigate the nephrotoxic effects of AZM and the possible ameliorative effects of vitamin E and sodium selenite in a rat model.Methods Thirty adult male Wistar rats (180–200 g) were randomly allocated into five groups (n = 6): control, vitamin E (100 mg/kg/day), sodium selenite (0.25 mg/kg/day), AZM (30 mg/kg/day), and AZM + vitamin E + sodium selenite. All treatments were administered orally once daily for 14 days. Renal function biomarkers (serum urea and creatinine) and hemoglobin levels were assessed. Kidney tissues were analyzed for oxidative stress markers (MDA, ROS, protein carbonyl, 8-OHdG), inflammatory mediators (MPO, NO, TNF-α), and apoptotic markers (caspase-3, cytochrome-c, p53), together with histopathological examination and apoptotic staining. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).Results AZM administration significantly elevated renal function markers, oxidative stress indices, inflammatory cytokines, and apoptotic signaling, accompanied by marked histopathological injury and increased caspase-3 expression. Conversely, co-administration of vitamin E and sodium selenite markedly attenuated detected biochemical alterations, improved renal functions, and restored renal architecture.Conclusion Subacute AZM exposure induces significant functional and histopathological renal alterations. Co-administration of vitamin E and sodium selenite confers marked nephroprotection mediated through antioxidant and anti-apoptotic actions. These findings suggest combined therapeutic potential in attenuating AZM-induced renal toxicity.