Protective Effects of Olea europaea L. Leaves and Equisetum arvense L. Extracts Against Testicular Toxicity Induced by Metronidazole Through Reducing Oxidative Stress and Regulating NBN, INSL-3, STAR, HSD-3β, and CYP11A1 Signaling Pathways

Metronidazole (MTZ), a widely used antiamoebic and antibacterial drug, has been linked to male reproductive damage. The aim of this study was to investigate <i>Olea europaea</i> L. and <i>Equisetum arvense</i> L. ethanol extracts for the protection against testicular toxicity and male infertility caused by MTZ, and to characterize the underlying mechanisms. Forty-two male rats were divided into six groups. The animals in group 1 served as the controls and received a daily oral dose (1 mL) of the vehicle. The animals in group 2 received metronidazole at doses of 400 mg/kg. Group 3 was treated with <i>E. arvense</i> extract at doses of 100 mg/kg. Group 4 was treated with <i>O. europaea</i> leaf extract at doses of 400 mg/kg. Group 5 was treated with metronidazole and <i>E. arvense</i> extract at doses of 400 and 100 mg/kg, respectively. Group 6 was treated with metronidazole with <i>O. europaea</i> leaf extract at doses of 400 and 400 mg/kg, respectively. The rats were given a daily oral dose of different treatments for 60 days, after which the animals were euthanized to study the histopathological and molecular changes in the testis and the sperm count in the epididymis. The testosterone levels, MDA levels, and GSH contents were also assessed in the rats in all groups. The findings revealed that the MTZ treatment caused a substantial increase in MDA levels and upregulated the <i>NBN</i> gene expression relative to the control. Moreover, the MTZ treatment produced significant reductions in the sperm count and viability, testosterone levels, and GSH content, and downregulated the INSL-3, STAR, HSD-3β, and CYP11A1 gene expression compared to the control. The adverse effects in testicular tissue were significantly reduced in rats given the <i>O. europaea</i> leaves and <i>E. arvense</i> treatment. The findings may show that MTZ can enhance testicular toxicity and infertility, but both plant extracts can prevent these harmful consequences.