Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl₂)-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl₂ (6.5 mg/kg), and FA + CdCl₂. CdCl₂ treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl₂-induced oxidative damage through exhausting the cellular defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) and downregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression accompanied by increases of malondialdehyde and nitric oxide contents. Testicular inflammation was evident indicated by increased levels of interleukin-1β and tumor necrosis factor-α in CdCl₂-treated rats. CdCl₂ exposure also decreased the expression of the proliferating cell nuclear antigen and augmented apoptotic events associated with prominent histopathological alterations. However, FA coadministration mitigated the impaired hormonal level, apoptotic and inflammatory injuries elicited by CdCl_2, and maintained the oxidant/antioxidant balance in testicular tissue via Nrf2 activation. Practical applications: Cadmium is an environmental toxicant and known to cause adverse effects including reproductive toxicity. However, antioxidant application has been found to protect against heavy metals-mediated toxic effects. Here, we examined the potential protective efficacy of ferulic acid against cadmium-mediated testicular impairments through estimating the amount of cadmium in the testis, hormonal profile, oxidative status, inflammatory response, apoptotic and proliferating markers in addition to the histopathological alterations. The obtained findings revealed that ferulic acid supplementation was able to abolish the testicular damages coupled with cadmium exposure. The protective efficiency of ferulic acid may correlated with its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that ferulic acid may be used to ameliorate cadmium-induced testicular deficits.