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An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats

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Abstract

Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.

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Acknowledgements

The authors are thankful to Riphah International University for providing research facilities to carry out the research and Dr. Shahid Ali Shah, Assistant Professor for carrying out Western blot analysis for us. We thank Dr. Khaled M.A Hasnain prof. of pathology and clinical pathology, Faculty of Veterinary medicine, Director of Electron Microscope Unit, Assiut University, where he helped us in the histopathological examination, lesion scoring, writing and photographed the histopathology. We special thank Prof. Dr Farrukh Kamal for his support.

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Authors and Affiliations

  1. Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan

    Sadaf Yasmeen, Aslam Khan, Fareeha Anwar & Muhammad Furqan Akhtar

  2. Department of Pharmaceutics, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan

    Sidra Yasmeen

  3. Faculty of Pharmacy, Superior University, Raiwind Road, Lahore, Pakistan

    Shafeeq Ali Shah

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  1. Sadaf Yasmeen
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Contributions

SY carried out experimental work, and method and results writing, AK and FA designed and supervised the project and prepare the manuscript and data analysis. MFA, SY, SAS helped in the data analysis and critical revision of the drafted manuscript. All authors approved the final version of the manuscript.

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Correspondence to Aslam Khan.

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The animal study, along with experimental protocols, was approved by the Research Ethical Committee of Riphah International University Lahore (REC/RIPS-LHR) with the reference number REC/RIPS-LHR/2022/060.

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I; Dr. Aslam Khan, give my consent for information about the text; pictures published in the article will be freely available to the public when it is published.

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Yasmeen, S., Khan, A., Anwar, F. et al. An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats. Environ Sci Pollut Res 30, 95660–95672 (2023). https://doi.org/10.1007/s11356-023-29134-z

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