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open access eISSN 2093-3673

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Original Article

Anat Cell Biol 2023; 56(4): 526-537

Published online December 31, 2023


Copyright © Korean Association of ANATOMISTS.

Effect of Sofosbuvir on rats’ ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study

Neven A. Ebrahim1 , Hussein Abdelaziz Abdalla2,3 , Neimat Abd Elhakam Yassin4 , Aya Elsayed Maghrabia5 , Amira Ibrahim Morsy1

1Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 2Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt, 3Department of Medical Biochemistry, Faculty of Medicine, Taibah University, Medina, Saudi Arabia, 4Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 5Veterinary in Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Correspondence to:Neven A. Ebrahim
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
E-mail: nevenebrahim@mans.edu.eg

Received: March 21, 2023; Revised: June 14, 2023; Accepted: June 22, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.

Keywords: Ovary, Sofosbuvir, Oxidative stress, Apoptosis, Vitamin E

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