Possible protective effects of vanillin against stress-induced seminiferous tubule injury via modulation of Nrf2 and ZO1

Around 20% of the human population is distressed. Previous studies have looked into the relationship between restraint immobilization stress (IS) and sexual behavior in male rats. The current study aimed to provide a brief explanation of the mechanisms that generated testicular injury with chronic IS and an attempt to evaluate the mechanisms and effects of vanillin as a novel protective agent. Forty-eight adult male albino rats were divided into six groups: control, vanillin-treated, chronic 2-h IS, 2-h stressed-vanillin-treated, chronic 6-h IS, and 6-h stressed-vanillin treated. The rats were sacrificed, and blood samples were collected for biochemical study. The testes were processed for biochemical and histological study, as well as histological Johnsen score. The results showed that prolonged IS increased both corticosterone and TNF-α levels as well as decreased testosterone, luteinizing hormone, catalase, and Nrf2 levels. This effect was more pronounced after 6 h of IS compared to 2 h. It also induced various testicular injuries with weak ZO-1 and CD34 immunoreactions. On the contrary, vanillin improved all mentioned biochemical and histological alternations induced by stress. Additionally, computational molecular docking analyses were conducted on the compound vanillin within the active site of Zona Occludens-1 (PDB ID: 2JWE). The results demonstrated remarkable docking scores and binding affinity, corroborating its potential protective efficacy. It could be concluded that vanillin is a promising treatment alternative for protecting testicular tissue from the harmful effects of IS via its antioxidant and anti-inflammatory properties.