Effect of L-Citrulline Supplementation on Cadmium-Induced Testicular Dysfunction in Male Albino Rats: Inhibition of Oxidative Stress and Apoptosis

Background and Objective: Exposure to cadmium (Cd) has been found to negatively affect the reproductive activities of male albino rats. This is mostly due to the involvement of oxidative stress and apoptotic pathways. This study aims to evaluate the preventive benefits of L-Citrulline (L-Cit) supplementation in mitigating testicular dysfunction resulting from Cd exposure. Materials and Methods: A total of 32 fully developed male albino rats were divided into four groups using a random assignment method. The groups were as follows: Control group, L-Cit group (administered with a dosage of 900 mg/kg), Cad group (administered with a dosage of 5 mg/kg) and L-Cit+Cad group. The treatments were orally delivered for 30 consecutive days. Post-treatment, the levels of serum testosterone, testicular nitric oxide (NO), oxidative stress indicators and sperm parameters were evaluated. Testicular tissue integrity and apoptosis were assessed using histopathological and immunohistochemical studies. Results: Exposure to Cd led to a significant drop in blood testosterone levels and an increase in oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and lower activity of antioxidant enzymes (SOD, CAT and GSH). On the other hand, L-Cit administration significantly improved testosterone levels, increased NO production and reduced oxidative damage. The histopathological study revealed that the L-Cit+Cad group had intact testicular structure and was associated with lower levels of caspase-3 expression, indicating a decrease in apoptosis. In addition, L-Cit enhanced sperm motility and viability while reducing morphological defects. Conclusion: The supplementation of L-Citrulline has been shown to have antioxidant and anti-apoptotic effects, significantly reducing reproductive failure caused by cadmium in male albino rats. These data indicate that L-Cit may have the potential as a therapeutic agent for treating heavy metal toxicity in male reproductive health.