Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt.
Zoology Department, Faculty of Science, Aswan University, Aswan, Egypt.
Hum Exp Toxicol. 2020 Jun;39(6):834-847. doi: 10.1177/0960327119867755. Epub 2020 Jan 30.
We aimed to explore the possible neurotoxicity and infertility mechanisms of prolonged metronidazole (MTZ) use and the effects of antioxidant grapefruit (GP) co-therapy on MTZ-induced complications. Sixty male albino Wistar rats were divided into four groups ( = 15 each). Group I (control group) received 1% dimethyl sulfoxide (27 ml/ kg/day), group II (MTZ group) received MTZ (400 mg/kg/day), group III (MTZ + GP) received MTZ (400 mg/kg/ day) plus GP juice (27 ml/kg/ day) and group IV (GP group) received GP juice (27 ml/kg) for 60 days. Semen analyses were performed. Free testosterone, gonadotrophin (follicle-stimulating hormone (FSH) and luteinizing hormone) and thiamine levels were measured. Samples of cerebellar, testicular and epididymal tissues were used for both colorimetric assays of oxidative stress markers and histopathological examinations. Significant decreases in the sperm count, percent total sperm motility, serum thiamine levels, free testosterone levels and FSH levels were observed in the MTZ and MTZ + GP groups ( < 0.05 for all parameters). Significantly higher oxidative stress levels ( < 0.05) were observed in the cerebellar and testicular tissue homogenates of these groups than in those of the control group, and associated disruptions in the cerebellar, testicular and epididymal structures were apparent compared to those of the control group. Although the GP group showed a significantly higher sperm count and significantly lower oxidative stress than the control group ( < 0.05), with histological similarity to the control group, the GP group exhibited significantly higher prolactin levels and lower free testosterone and FSH levels than the control group ( < 0.05). Oxidative stress and decreased thiamine levels could explain the MTZ-induced neurotoxicity and infertility side effects that aggravated by GP co-administration.
我们旨在探索长期使用甲硝唑（MTZ）可能的神经毒性和不育机制，以及抗氧化葡萄柚（GP）联合治疗对 MTZ 诱导的并发症的影响。将 60 只雄性白化 Wistar 大鼠分为四组（每组 15 只）。第 I 组（对照组）给予 1%二甲亚砜（27 ml/kg/天），第 II 组（MTZ 组）给予 MTZ（400 mg/kg/天），第 III 组（MTZ+GP 组）给予 MTZ（400 mg/kg/天）+GP 汁（27 ml/kg/天），第 IV 组（GP 组）给予 GP 汁（27 ml/kg/天），共 60 天。进行精液分析。测定游离睾酮、促性腺激素（卵泡刺激素（FSH）和黄体生成素）和硫胺素水平。取小脑、睾丸和附睾组织样本进行比色法测定氧化应激标志物和组织病理学检查。MTZ 组和 MTZ+GP 组的精子计数、总精子活力百分比、血清硫胺素水平、游离睾酮水平和 FSH 水平均显著下降（所有参数均 <0.05）。这些组的小脑和睾丸组织匀浆中的氧化应激水平明显升高（<0.05），与对照组相比，小脑、睾丸和附睾结构明显紊乱。虽然 GP 组的精子计数明显高于对照组，氧化应激明显低于对照组（<0.05），组织学与对照组相似，但 GP 组的催乳素水平明显高于对照组，游离睾酮和 FSH 水平明显低于对照组（<0.05）。氧化应激和硫胺素水平降低可能解释了 MTZ 诱导的神经毒性和不育副作用，而 GP 联合治疗加重了这些副作用。
