Ethanol Leaf Extract of Baphia longipedicellata Ameliorates Metronidazole-Induced Oxidative Stress and Cytoarchitectural Alterations in the Hypothalamic-Pituitary Axis of Male Wistar Rats

The hypothalamic–pituitary axis regulates reproduction, and its oxidative-stress vulnerability is key to reproductive toxicity from drugs. Metronidazole (MTZ) has been associated with adverse effects on this axis, potentially impairing male fertility. This study investigated the protective effects of ethanol leaf extract of Baphia longipedicellata (ELEBL) against metronidazole-induced oxidative stress and cytoarchitectural alterations in the hypothalamic-pituitary axis of male Wistar rats. Twenty-five adult male Wistar rats (190-210g) were divided into five groups (n=5). Group A received distilled water (10 mL/kg). Group B received MTZ (500 mg/kg) for 14 days. Groups C and D received MTZ followed by ELEBL at 200 mg/kg and 400 mg/kg respectively for 54 days. Group E received MTZ with a 54-day withdrawal period. After treatment, hypothalamic-pituitary tissues were harvested and evaluated for oxidative stress biomarkers (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA). Histoarchitecture was assessed using Hematoxylin and Eosin (H&E) and Cresyl Fast Violet staining. MTZ administration significantly depleted SOD, CAT, and GSH while elevating MDA levels compared with controls (p<0.0001). ELEBL at both doses significantly restored antioxidant enzyme activities and reduced MDA to near-control values (p<0.05), with the 400 mg/kg dose demonstrating superior efficacy. Histological examination revealed that MTZ caused severe neuronal degeneration, vacuolation and pyknosis in the hypothalamus, along with marked degeneration of acidophils and basophils in the pituitary gland. ELEBL-treated groups showed near-normal architecture with preserved Nissl substance and well-distributed pituitary cell populations. These findings demonstrate that ELEBL attenuates metronidazole-induced oxidative stress and preserves hypothalamic-pituitary cytoarchitecture.