Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

Abstract

Several organ systems can be affected by nicotine/cigarette smoking (CS); however, there is a gap of knowledge about the role of local neurotransmitter system, brain-derived neurotrophic factor (BDNF), and dopamine (DA) in testicular toxicity. Therefore, the aim of the present study is to explore the toxic impact of short- and long-term exposure to oral nicotine and passive CS on adult albino Wistar rats, using doses that closely mimic the human smoking scenario. Our results showed dose- and time-dependent loss of developing spermatogonia and spermatocyte of the seminiferous tubules, disruption of basement membrane, DNA damage, and high serum cotinine upon exposure to nicotine and CS, resulting in low sperm count as compared to control. Further, the results showed the upregulation of BDNF, DA, tyrosine hydroxylase (TH), and pro-oxidants, ie, reactive oxygen species (ROS) and inducible nitric oxide synthetase (iNOS), in the exposed testis and downregulation of the antioxidants such as, ascorbate and Nrf2 when compared with the control. Thus, our results for the first time highlight a potential role of the local neurotransmitter system and antioxidant depletion (Nrf2) in nicotine/CS-induced testicular pathogenesis, which could underpin the development of therapeutic interventions targeted at oxidative stress-associated disorders, and probably establish a link with the brain system contributing to addiction.