Abstract
Testicular degeneration represents a severe pathological condition characterized by impaired spermatogenesis, disruption of endocrine function, and consequent reduction in male fertility. Cadmium chloride (CdCl₂) is a well-established environmental toxicant that induces pronounced reproductive toxicity through the induction of oxidative stress, hormonal imbalance, and progressive deterioration of testicular architecture. Accordingly, the present study was designed to evaluate the therapeutic efficacy of kappa-opioid receptor (KOR) blockade using Nor-binaltorphimine (Nor-BNI), in comparison with Vitamin C, in ameliorating cadmium chloride-induced testicular degeneration in male rats.
A total of thirty-two adult male albino rats were randomly allocated into four equal groups (n = 8 per group). Testicular degeneration was induced by intraperitoneal administration of cadmium chloride (1 mg/kg body weight) once weekly for two consecutive weeks. Following a three-day interval after the final cadmium dose, treatment was initiated. Vitamin C was orally supplied at a dosage of 100 mg/kg per day for 28 successive days, while Nor-binaltorphimine (Nor-BNI) was supplied intraperitoneally at a dosage of 10 mg/kg. Total duration of the experiment was 39 days.
The levels of FSH, LH, GnRH, and testosterone in serum samples were quantified using an ELISA assay, while LHR gene expression was quantified using RT-qPCR technique. Sperm parameters were assessed to evaluate their fertility.
Exposure to cadmium was associated with a marked decrease in reproductive hormones' level, LHR gene down-regulation, and changes in sperm characteristics (P < 0.05). Treatment with Nor-Binaltorphimine (Nor-BNI) resulted in a significant enhancement of sperm functional parameters, including sperm motility and progressive motility; in turn, Vitamin C had only a moderate effect. The obtained data point to a higher efficacy of Nor-BNI in terms of restoration of reproductive parameters, presumably due to better regulation of the HPG axis by the neuroendocrine mechanism.

Key words: Testicular degeneration; Cadmium chloride; Vitamin C; Nor-binaltorphimine; kappa-opioid receptor