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

Cell Physiol Biochem. 2024 Dec 13;58(6):722-738. doi: 10.33594/000000745.

Abstract

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.

Keywords: Cranberry ; Vitamin-C ; Phenobarbital ; Fertility ; Testis ; Spermatozoa.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Ascorbic Acid* / pharmacology
  • Caspase 3* / metabolism
  • Catalase* / metabolism
  • Glutathione / metabolism
  • Male
  • Malondialdehyde* / metabolism
  • Oxidative Stress / drug effects
  • Phenobarbital* / toxicity
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar*
  • Superoxide Dismutase* / metabolism
  • Testis* / drug effects
  • Testis* / metabolism
  • Testis* / pathology
  • Vaccinium macrocarpon* / chemistry

Substances

  • Phenobarbital
  • Superoxide Dismutase
  • Malondialdehyde
  • Catalase
  • Caspase 3
  • Ascorbic Acid
  • Glutathione
  • Plant Extracts
  • Antioxidants