Comparative Uterine Histopathology of Diazepam and Elaeis guineensis Co-administration in a Murine Model

Abstract

Background: Diazepam, a commonly prescribed benzodiazepine, is used by some women of reproductive age, while Elaeis guineensis (oil palm) is consumed as food and used in traditional medicine. Although both substances may influence reproductive tissues, their combined effects on uterine histology, particularly according to administration sequence, remain inadequately described. Objective: This study evaluated comparative uterine histopathological changes in female mice following co-administration of diazepam and Elaeis guineensis extract, with emphasis on the effect of the order of administration. Methods: Sixteen adult female mice weighing 25-40 g were assigned to four groups (n = 4): Group A (control), Group B (E. guineensis followed by diazepam 2 hours later), Group C (diazepam followed by E. guineensis 2 hours later) and Group D (diazepam alone). Diazepam was administered orally at 18.75 mg/mL for 28 days. At the end of the experiment, uterine tissues were collected, fixed in 10% formalin, processed for routine histology, stained with haematoxylin and eosin and examined microscopically. Results: Group A showed normal uterine histology, with no evidence of necrosis or inflammation. Group B showed mild intravascular erythrocyte accumulation without haemorrhage or fibrosis. Group C showed severe extravascular haemorrhage, while Group D showed haemorrhage with fibrotic remodelling. Necrosis and inflammation were not observed in any group. Conclusion: Diazepam exposure was associated with uterine vascular alterations ranging from erythrocyte accumulation to haemorrhage and fibrosis. Prior administration of E. guineensis appeared to reduce diazepam-associated uterine damage, whereas administration after diazepam showed limited protective effect. The findings suggest a sequence-dependent drug-herb interaction that warrants further mechanistic and reproductive outcome studies.