Co-Treatment with Cranberry and Vitamin-C Mitigates Reproductive Toxicities Induced by Phenobarbital in Male Rats

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Background/Aims: 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. Methods: 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. Results: 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. Conclusion: 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.