Paracetamol-Associated Testicular Microarchitectural Disturbances and Their Histological Amelioration by Rutin and Mesenchymal Stem Cells in Male Rats

Abstract

Paracetamol (PCM) is widely used as an analgesic and antipyretic agent, but excessive exposure may induce tissue injury beyond the liver, including alterations in testicular structure. This study investigated the histopathological effects of PCM on the testes of adult male rats. It evaluated the ameliorative potential of rutin (RUT) and bone marrow-derived mesenchymal stem cells (BM-MSCs), administered separately or in combination. Fifty adult male albino rats were randomly allocated to control and experimental groups. PCM was administered orally at 750 mg/kg body weight every 72 h for three weeks. Following PCM exposure, rats received RUT (25 mg/kg/day), a single intravenous dose of BM-MSCs (1.5 × 10⁶ cells), or both treatments for one or two months. PCM exposure produced progressive testicular damage characterized by seminiferous tubular degeneration and atrophy, reduced tubular diameter, vascular congestion, interstitial oedema, disruption of the germinal epithelium, and marked reduction or absence of spermatogenesis. RUT treatment promoted gradual structural recovery, whereas BM-MSC administration produced more evident preservation of seminiferous architecture and spermatogenic activity. The combined treatment resulted in the greatest histological improvement, with testicular organization approaching that of controls after two months. These findings indicate that RUT and BM-MSCs may have therapeutic potential against PCM-induced testicular injury, particularly when used in combination.