Adverse Effects of Hydroxychloroquine on Testicular Tissue and Sperm Quality: An Experimental study on Male Albino Rats

Introduction: Hydroxychloroquine (HCQ) is a medicine that has mainly been used to treat malaria. During the recent Coronavirus Disease-2019 (COVID-19) period, an abrupt spike in the sale of HCQ has been found. The repurposing of this drug in the treatment of COVID-19 was not only found to be ineffective but also showed many side effects. The adverse effects of the enormous exposure to this drug should be unveiled. Aim: To evaluate the acute effect of HCQ exposure on the male reproductive system by analysing the changes in antioxidant enzyme levels in testicular tissue, sperm quality, and histopathological assessment of testicular tissue using male albino rats as the subject model. Materials and Methods: The present experimental study was done by using male albino rats as the subject model. It was conducted in the laboratory of the Department of Human Physiology at Raja NL Khan Women's College (Autonomous) in Medinipur, West Bengal, Kolkata, India, from the last week of June 2023 to the first week of August 2023. A total 10 male albino rats were obtained and randomly divided into two groups (n=5 in each group), control and HCQ-treated, and were given plain drinking water and 33 mg/kg/day HCQ, respectively, for six consecutive days through oral gavage. After the treatment tenures, rats were euthanised, and antioxidant enzymatic activity was measured by a spectrophotometer. Sperm quality and testicular histopathology were studied. A two-tailed t-test was used to compare the parameters of the control and HCQ-treated groups. Results: The total testicular weight of the control group was 2.37 +/- 0.17 g, in contrast treated group had a significantly lower testicular weight of 1.98 +/- 0.19 g. A significant decrease in total testicular protein in the treated group was found, i.e., 28.86 +/- 3.03 mg/g of tissue, compared to the control group, i.e., 60.46 +/- 2.85 mg/g of tissue. The sperm count of the control group was 4.51 +/- 0.06 million/ml of suspension, while the treated group had a significantly lower sperm count, i.e., 2.73 +/- 0.11 million/mL of suspension. The percentages of sperm motility and viability in the control group were 86 +/- 1.63% and 94 +/- 1.33%, respectively, but in the treated group, the percentages were significantly lower, i.e., 22.66 +/- 1.35% and 24 +/- 1.78%, respectively. The increasing sperm anomalies after HCQ exposure indicate poor sperm quality. Conclusion: Infertility or reduced fertility can result from testicular dysfunction, in continuation, decrease in sperm count, motility, viability, together with abnormalities in sperm morphology, was observed after this exposure. Thus, the present study provides insight into the adverse effects of the use of this drug, which might be associated with male infertility.