Allicin attenuates doxorubicin-induced testicular and systemic toxicity in rats via antioxidant and anti-apoptotic mechanisms.

The clinical use of doxorubicin (DOX) is limited by toxicity in rapidly dividing tissues, notably the testes. This study evaluated allicin as a protective agent against DOX‑induced reproductive toxicity in male rats. Thirty-six male Sprague Dawley rats were randomly divided into six groups (n = 6): Group 1 received saline; Group 2 received DOX (a cumulative dose of 7.5mg/kg, i.p. on days 8, 11, and 14); Group 3 received allicin alone (dissolved in corn oil, 20mg/kg/day, orally for 14 days); Group 4 received DOX + allicin (10mg/kg/day); Group 5 received DOX + allicin (20mg/kg/day); and Group 6 received corn oil as the vehicle control. DOX treatment induced severe oxidative stress (OS), as evidenced by a 6.5-fold increase in malondialdehyde (MDA) and an 83% decrease in superoxide dismutase (SOD) activity, indicating lipid peroxidation and impaired antioxidant defence. Allicin coadministration reduced MDA by 47% and recovered SOD activity to 73% of the control level. Furthermore, the TUNEL assay revealed a 4.6-fold increase in apoptotic index in DOX-treated rats, which allicin significantly attenuated dose-dependently. DOX upregulated MMP-9 (3.1-fold) and downregulated Cx43 and mTOR to 15% and 18% of the control levels, respectively, while allicin normalized these levels. Reproductive outcomes were compromised by DOX, with a 38% decline in sperm count, a 65% reduction in viability, a 93% drop in testosterone, and a 51% increase in morphological abnormalities; allicin improved these metrics by up to 60%. Hematologically, DOX induced pancytopenia, which was partially reversed by allicin, resulting in an increase in leukocytes, erythrocytes, and platelets. In summary, allicin ameliorated DOX‑induced testicular and systemic toxicity through antioxidant, anti‑apoptotic, and gene‑regulatory mechanisms.