The Effect of Remdesivir as An Anti-COVID-19 Drug on the Secretion of Inflammatory Markers by Chicken Liver Cells: An In Vitro Study

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.

Keywords

• hepatocytes
• covid-19
• remdesivir
• inflammatory factors