Promethazine induces testicular and epididymal toxicity via the upregulation of xanthine oxidase/uric acid-mediated oxidative stress signaling

Promethazine is a pharmacological compound classified as a first-generation antihistamine. It is often used in the treatment of a range of medical ailments, including allergies, insomnia and the common cold. The primary objective of this study was to evaluate the impact of promethazine on the structural integrity of the testes, levels of testosterone in the circulatory system, the process of spermatogenesis and the quality of sperm. This study aim to investigate the potential involvement of oxidative stress-dependent pathway, cytokines, caspase-3 and xanthine oxidase activities and uric acid levels. A total of twenty adult male Wistar rats were randomly assigned to two groups, each consisting of ten rats. The control group was given 0.5 ml of distilled water orally as a vehicle for a duration of 56 days. The promethazine-treated group, on the other hand, received a dosage of 50 mg/kg of promethazine hydrochloride over the same 56-day period. The administration of promethazine resulted in compromised steroidogenesis and spermatogenesis, ultimately leading to diminished sperm quality. Concomitant with this phenomenon, there was an increase in the indicators of testicular damage, oxidative stress, xanthine oxidase/uric acid levels, inflammation and apoptosis. Furthermore, there was a notable decrease in the functioning of enzymatic antioxidants in the testicles. A change in testicular cytoarchitecture, as well as a decrease in both absolute and relative testicular weight, accompanied these modifications. Therefore, it may be deduced that promethazine elicits testicular harm via the overexpression of xanthine oxidase and uric acid, as well as the activation of caspase-3 through an oxidative-sensitive signaling route.