Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic–pituitary–gonadal axis by inducing oxidative stress.

Risperidone (RIS), a commonly used drug during a lifetime for the treatment of schizophrenia, causes some adverse effects in the male reproductive system; however, there is no comprehensive reproductive toxicity study of RIS. For this purpose, male rats were administered orally for 1.25, 2.5 and 3 mg/kg RIS for 28 days and the sperm count, motility, morphology, DNA damage and the histological changes in testicular tissue were evaluated. Follicle‐stimulating hormone (FSH), luteinising hormone (LH) and serum levels of testosterone, which are the main hormonal regulators of reproduction, and testicular glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels as the indicators of oxidative stress were determined. Normal sperm morphology was decreased in RIS groups and histopathological degeneration occurred in testis tissue dose‐dependently. Serum LH levels were not altered; however, FSH and testosterone levels decreased in the high‐dose group. Histopathologic examination showed RIS toxicity targeted Leydig cells, which might be associated with impairment of the hypothalamic–pituitary–gonadal (HPG) axis. GSH levels were decreased and MDA levels were increased in the high‐dose group which was evaluated as indicators of oxidative stress. In conclusion, RIS caused reproductive toxicity in male rats by inducing oxidative stress and disrupting hormonal regulation. [ABSTRACT FROM AUTHOR]