Neven A Ebrahim, Hussein Abdelaziz Abdalla, Neimat Abd Elhakam Yassin, Aya Elsayed Maghrabia, Amira Ibrahim Morsy
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引用次数: 0
Abstract
Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.
丙型肝炎病毒(HCV)感染是全球范围内的一大健康问题,根除该病毒是当务之急。直接作用的丙型肝炎病毒聚合酶抑制剂,如索非布韦(SOF),是一种有效的治疗方案。然而,它也有一些副作用,如诱变、致癌和损害睾丸功能。由于目前还没有相关研究,因此评估索非布韦对卵巢的安全性非常重要。增加活性氧(ROS)的产生会导致氧化应激,从而影响排卵过程、女性生殖和生育能力。事实证明,细胞中的 SOF 积累会促进 ROS 的产生。维生素 E(Vit E)是一种抗氧化剂,在女性生殖系统中发挥着重要作用,缺乏维生素 E 可导致不孕。我们通过生化和免疫组化实验研究了单独处理 SOF 和与 Vit E 联合处理对卵巢 ROS 水平和卵巢形态的影响。结果表明,氧化应激标志物(一氧化氮和丙二醛脂质过氧化反应)、抗氧化酶(过氧化氢酶、超氧化物歧化酶和还原型谷胱甘肽)、增殖标志物(增殖细胞核抗原和 Ki-67 抗原)以及 caspase 3 细胞凋亡标志物均发生了显著变化。结果表明,当 SOF 诱导氧化应激时,也会加重卵巢功能障碍。研究还显示,维生素 E 作为一种抗氧化剂,在保护卵巢组织免受氧化应激标记物的影响并保持其功能方面发挥着重要作用。这可以指导人们在 SOF 方案中添加维生素 E 补充剂,以限制其对卵巢功能的伤害。