Riboflavin Recovery of Spermatogenic Dysfunction via Dual Inhibition of Oxidative Changes and Regulation of the PINK1-Mediated Pathway in an Arsenic-Injured Rat Model
Background: Arsenic trioxide (As2O3) poisoning and associated potential lesions are of global concern. Inversely, riboflavin (vitamin B2, VB2) a component of flavoproteins could play a vital role in the enzymatic reactions. Thus, this research aimed to explore the potential beneficial roles of VB2 during As2O3-injured-toxicity. Methods: Adult male rats were challenged as follows: 3 mg As2O3/L and 40 mg VB2/L alone or in combination administered in drinking water, for 30 consecutive days. Daily basis As2O3 and VB2 dissolved in deionized water for 5 min (gradually and slowly). Malondialdehyde (MDA), Glutathione Peroxidase (GSH), Superoxide dismutase (SOD), and Catalase (CAT) were computed for oxidative stress, and TAS (Total Antioxidative Status) levels were computed for the antioxidant system, for both serum and tissue. Apoptosis levels were assessed in the evaluation of testis gene expression. P<0.05 was considered statistically significant. Results: The results show that As2O3 significantly decreased the body weight, testicular weight and volume, semen quality and testicular cell count (p<0.05). Furthermore, malondialdehyde (MDA) content in the testicular tissue of the As2O3 group rats was significantly higher in comparison to the vehicle group (p<0.05). Likewise, TAS C) and the activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) were reduced (p<0.05) when compared to the control. As2O3 induced testicular damage and seminiferous tubular atrophy. Monodansylcadaverine (MDC) assays mimicking the histopathology observations. Meanwhile, As2O3 upregulated the expression of mitophagy-related genes including PINK1, Parkin, USP8, LC3-I, Fis1, and Mfn2. However, p38, responsible for stress stimuli, was also upregulated by As2O3 administration. Conclusions: Our study revealed that VB2 supplementation protected testicular structures against As2O3-induced injury via dual inhibition of oxidative changes and regulation of the PINK1-mediated pathway. Therefore, our experiments provide a new mechanistic scheme with respect to As2O3-induced male reproductive system toxicity.