Ebrahim Neven A, Abdalla Hussein Abdelaziz, Yassin Neimat Abd Elhakam, Maghrabia Aya Elsayed, Morsy Amira Ibrahim
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Anat Cell Biol. 2023 Dec 31;56(4):526-537. doi: 10.5115/acb.23.079. Epub 2023 Sep 1.
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）感染是全球主要的健康问题，根除该病毒势在必行。直接作用的HCV聚合酶抑制剂，如索磷布韦（SOF），是一种有效的治疗方案。然而，它有一些副作用，如诱变、致癌和睾丸功能损害。由于目前尚无相关研究，评估SOF对卵巢的安全性很重要。活性氧（ROS）生成增加会导致氧化应激，影响排卵过程、女性生殖和生育能力。已证明细胞中SOF的积累会促进ROS生成。维生素E（Vit E）是一种抗氧化剂，在女性生殖系统中起重要作用，其缺乏会导致不孕。我们通过生化和免疫组化研究，实验性地探讨了单独使用SOF以及与Vit E联合治疗对卵巢ROS水平和卵巢形态的影响。氧化应激标志物（一氧化氮和丙二醛脂质过氧化）、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）以及半胱天冬酶3凋亡标志物均出现显著变化。结果表明，SOF在诱导氧化应激的同时，也加剧了卵巢功能障碍。还显示了Vit E作为抗氧化剂在保护卵巢组织免受氧化应激标志物影响并维持其功能方面的重要作用。这可为在SOF治疗方案中添加Vit E补充剂以限制其对卵巢功能的有害影响提供指导。
