The Preventive Effect of Zinc Sulfate against Olanzapine-Induced Testicular Toxicity in Male Rats

Male infertility is a complex and multifactorial clinical condition affecting a large population attributed to several factors, including perturbation in oxidative stress and the level of essential trace elements. Oxidative stress exerts multiple issues related to reproductive health, including male infertility, decreased sperm motility, sperm DNA damage, and an increased susceptibility to genetic disorders. Besides chemical toxins and food allergens in junk food items, many drugs can also lead to male infertility. Olanzapine (OLZ), a general antipsychotic drug, has also been reported to induce male fertility. A great deal of literature entails that supplementation of zinc can alleviate oxidative stress-related clinical complications, including male infertility. This study investigates the potential protective effects of zinc sulfate (ZnSO4) on OLZ-induced male infertility. In the present study, there were four treatment groups (n = 6): group 1 as control (without any treatment); group 2 treated with OLZ (10 mg/kg) orally daily for 6 weeks; groups 3 and 4 treated with 50 mg/kg and 100 mg/kg of ZnSO4 respectively in pre-exposed OLZ (10 mg/kg) orally daily for 6 weeks. After completion of the treatment, the biochemical analysis of serum and tissue samples demonstrated that group 2 had compromised levels of antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)) as well as elevated levels of stress parameters (oxidized glutathione (GSSG), malondialdehyde (MDA), and nitric oxide (NO)) as compared to the control by a significant extent (p ≤ 0.05). However, supplementation of ZnSO4 significantly corrected all these parameters in a dose-dependent way in groups 3 and 4 (p ≤ 0.05). Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, and vitamin E, were also observed to improve prominently with the supplementation of ZnSO4. Intriguingly, all the fertility parameters (sperm motility, count and level of testosterone) were also found to be significantly enhanced with decreased sperm abnormalities in both the combination groups. The histological evaluation of the testis section also agreed with the biochemical analysis in this investigation. Therefore, the study strongly advocates that supplementation of Zn can ameliorate OLZ-induced male infertility to a significant extent.