Evaluation of reproductive and renal toxicity of varenicline in male rats

Objective(s): Varenicline is a selective partial agonist for the nicotinic acetylcholine receptor a4b2 subtype, which is widely used to treat smoking addiction. However, there is still no data about its potential toxic effects on tissues. In this study, we aimed to determine the varenicline-induced toxicity on reproductive and renal tissues in rats. Materials and Methods: Rats were randomly divided into two groups: control (n=10) and varenicline (n=24). Then, rats in each group were sub-divided equally as acute and chronic groups. The control rats were orally given distilled water only. Varenicline was administrated orally as follows: 1st–3rd days 9 μg/kg/day, 4th–7th days 9 μg/kg twice daily, and 8th–90th days 18 μg/kg twice daily. The rats of acute and chronic groups were sacrificed on the 45th and 90th days, respectively. Some tissue markers related to oxidative stress were measured, and sperm characteristics were observed. Results: In the acute group, varenicline led to a significant decrease in SOD activities in both kidney and testis tissues. In the chronic group, varenicline significantly increased MDA and MPO production, and reduced CAT and GPx levels in the kidneys and testes. Also, SOD and GSH levels significantly decreased in the testes. Moreover, sperm characteristics were negatively affected; histopathological deformation was observed in the testes and kidneys in all groups. Conclusion: This study showed that varenicline could detrimentally affect the kidneys and testes in both acute and chronic term usage. Further studies will provide more insights into the molecular dynamics of this damage.