Contrasting renal effects of metformin and allicin in doxorubicin-induced nephrotoxicity in experimental animals

Doxorubicin (DOX) remains a cornerstone in cancer chemotherapy; however, its therapeutic benefit is often compromised by progressive organ toxicity, with renal impairment representing a major clinical concern. Although metformin at conventional doses has been associated with renoprotective actions mediated by redox and inflammatory modulation, the renal safety profile of supratherapeutic dosing is still debated. Allicin, a garlic-derived organosulfur molecule, has attracted attention due to its strong antioxidant and tissue-protective capabilities. In this experimental investigation, the renal responses to high-dose metformin and allicin, either alone or combined, were examined in a DOX induced nephrotoxicity model. Adult male Wistar rats (n = 70) were distributed across seven study arms comprising untreated controls, DOX treated animals, metformin-treated animals, allicin-treated animals, and three combination regimens involving DOX with metformin, allicin, or both agents. Doxorubicin was administered intraperitoneally at spaced intervals to achieve a cumulative exposure of 18 mg/kg, while metformin (300 mg/kg day) and allicin (40 mg/kg/day) were delivered orally throughout a 21-day period. At the end of the experimental protocol, comprehensive biochemical, oxidative, inflammatory, and histological assessments were performed. Administration of high-dose metformin resulted in marked deterioration of renal status, reflected by worsened functional indices, impaired antioxidant capacity, intensified lipid peroxidation, suppression of nitric oxide availability, and extensive structural damage, surpassing alterations induced by DOX alone. In contrast, allicin markedly mitigated renal injury associated with both DOX and metformin, leading to biochemical improvement and preservation of renal tissue integrity. Collectively, these results indicate that excessive metformin dosing may potentiate renal toxicity, whereas allicin demonstrates a robust protective effect against drug-related renal injury.