Mechanistic insights into the protective effects of vitamin E against olanzapine-induced testicular toxicity: The role of microRNAs in oxidative stress and apoptosis.

OBJECTIVES

Research on the male gonadotoxic effects of olanzapine (OLZ) and the potential protective role of vitamin E (Vit E) remains limited. This investigation aimed to assess the toxic impact of OLZ on the testes' integrity and the protective role of dietary Vit E.

MATERIALS AND

METHODS

In this experimental study, twenty-eight rats were divided into four groups: a control group, a group administered 5 mg/kg of OLZ orally, a group receiving both OLZ and 100 mg/kg of Vit E, and a group treated with Vit E alone. We assessed testes dimensions, structural alterations, serum concentrations of testosterone and prolactin, sperm parameters, oxidative stress, and apoptosis. Additionally, the expression levels of microRNA (miR)-122 and miR-202-5p were quantified.

RESULTS

Administration of OLZ resulted in significant structural damages to the testes characterized by apoptosis, cellular stress, and disruption of miR-122 and miR-202-5p expression. Otherwise, Vit E restores the histological structure, apoptosis, and sperm quality affected by OLZ. Notably, hormonal profiles and indices of cellular stress showed significant improvement in rats receiving a combination of Vit E and OLZ. Furthermore, the expressions of miR-122 and miR-202-5p were normalized in the OLZ+Vit E treated group.

CONCLUSION

This study highlights the protective role of dietary Vit E against OLZ-induced testicular toxicity by enhancing testicular histo-architecture, reducing stress markers, and modulating of microRNA expressions.