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  • Co-Treatment with Cranberry and Vitamin-C Mitigates Reproductive Toxicities Induced by Phenobarbital in Male Rats. El-Rahman, Heba Ali Abd Hasan, Ahmed Flayyih Alyasiri, Thura El-Wahsh, Hany M Althubyani, Sarah A Basyony, Mohamed A El-Naggar, Sabry Ali Mahmod, Doha Hanafy Animals Male Phenobarbital Rats, Wistar Testis Vaccinium macrocarpon Rats Superoxide Dismutase Malondialdehyde Catalase Caspase 3 Ascorbic Acid Glutathione Plant Extracts Antioxidants Oxidative Stress Apoptosis Phenobarbital (PB), commonly used for epilepsy management, is associated with testicular dysfunction after prolonged use. This study aimed to evaluate the ameliorative effects of cranberry (CB) and vitamin C (Vit-C) on PB-induced reproductive toxicity in rats. Forty male Wistar rats were divided into five groups. G1 was the negative control, while G2 received PB (160 mg/kg orally) for one month. Groups G3 and G4 received PB followed by CB (500 mg/kg) and Vit-C (27 mg/kg) treatments, respectively. G5 received PB followed by a combined CB and Vit-C regimen. The levels of catalase (CAT), superoxide dismutase (SOD), glutathione reduced (GSH), and malondialdehyde (MDA) were determined using standard biochemical assays. Histological changes in testicular tissues were assessed, and caspase-3 expression was quantified via immunohistochemistry. PB exposure increased MDA levels, reduced SOD and CAT activity, and disrupted testicular histology, with elevated caspase-3 expression indicating heightened apoptosis. Treatment with CB or Vit-C significantly restored antioxidant enzyme activities, reduced MDA levels, and ameliorated histological abnormalities. Co-treatment with CB and Vit-C yielded the most pronounced protective effects, including reduced caspase-3 expression and improved testicular structure. CB and Vit-C demonstrate significant protective effects against PB-induced testicular toxicity, likely due to their antioxidative and anti-apoptotic properties. Co-administration of these agents offers an effective strategy to mitigate reproductive toxicities associated with prolonged PB use.