The effect of remdesivir as an anti-covid-19 drug on the secretion of inflammatory markers by chicken hepatocytes: an in vitro study

Zahra Akbari Jonoush; Roya Mahdavi; Mehri Ghafourian; Seyed Esmaeil Khoshnam; Fereshteh Nezhad Dehbashi; Maryam Farzaneh

Journal of Inflammatory Diseases

The Official Journal of Qazvin University of Medical Sciences

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The effect of remdesivir as an anti-covid-19 drug on the secretion of inflammatory markers by chicken hepatocytes: an in vitro study

Author(s):

Zahra Akbari Jonoush¹,

Roya Mahdavi²,

Mehri Ghafourian³,

Seyed Esmaeil Khoshnam⁴,

Fereshteh Nezhad Dehbashi⁵,

Maryam Farzaneh^6,*

1Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

3Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

5Cellular and Molecular Research Center, Medical Basic Science Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

6Fertility, Infertility, and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Journal of Inflammatory Diseases:Vol. 26, issue 4; 173-182

Article type:Research Article

How to Cite:Zahra Akbari JonoushRoya MahdaviMehri GhafourianSeyed Esmaeil KhoshnamFereshteh Nezhad DehbashiMaryam Farzanehet al.The effect of remdesivir as an anti-covid-19 drug on the secretion of inflammatory markers by chicken hepatocytes: an in vitro study.J Inflamm Dis.26(4):e156324.

Abstract

Background: For severe cases of acute respiratory syndrome type 2 (SARS-CoV-2) infection (COVID-19), Remdesivir (RDV) is introduced as an anti-viral drug with side effects. Hepatotoxicity from prolonged exposure to RDV is associated with increased inflammatory factors. In this study, we evaluated the effect of RDV on the secretion of inflammatory markers by chicken liver cells. Methods: In this in vitro study, 20 stage X embryonated chicken eggs were incubated for 10 days at 37.5°C and 60–65% humidity Hamburger–Hamilton stages (stage HH35). Liver cells were grown in a medium containing DMEM/F12+10% fetal bovine serum (FBS). After three days, the culture media was supplemented with four doses of RDV (1.00, 2.00, 3.00, and 4.00 μM). After 24 and 48hs, the viability of the hepatocytes, gene expression of Sox17, CXC motif chemokine receptor 4 (CXCR4), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and TNF-α, and hepatocellular functions (albumin and urea secretion) were assessed. Findings: Each hepatocyte had a prominent nucleus and a nucleolus with a hexagonal shape. The pink tint of the periodic acid Schiff (PAS) positive cells in the PAS staining verified the hepatocytes’ glycogen content. Up to 50% of the cells lose viability after 48 hours in the presence of 3 and 4 μM RDV (P<0.001). In the presence of 3 μM RDV, the production and secretion of both albumin (P<0.001) and urea (P<0.05) decreased. Besides, the expression of IL-1, IL-6, and TNF-α significantly increased after treatment with 3 μM RDV (P<0.001). Conclusion: We concluded that RDV therapy altered the expression and function of hepatocyte inflammatory factors.

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