The Effect of Remdesivir as an anti-COVID-19 Drug on Chicken Hepatocyte Enzymes; an in vitro Study

Background and Aim: There is little in vitro evidence of potential hepatotoxicity of Remdesivir (RDV). Regarding the effective results of RDV in patients with COVID-19 and the impact of COVID-19 on liver function, we investigated the effects of RDV on the expression and activity of liver enzymes in chicken embryo-derived hepatocytes. Materials and Methods: In this in vitro study, 20 embryonated chicken eggs (stage X) were incubated (37.5 °C, 60-65% humidity) for 10 days (stage HH35). The hepatocytes were cultured in DMEM/F12+10% FBS medium and treated with four concentrations of RDV (2.00, 3.00, 4.00, and 5.00 µM). Serum levels of alanine (ALT) and aspartate (AST) aminotransferases were measured by enzyme-linked immunosorbent assay (ELISA), and gene expression was measured by quantitative real-time PCR (qPCR). Results: Each hepatocyte had a hexagonal structure with a large nucleus and nucleolus. In the PAS-positive cells with a pink color confirmed the glycogen content of hepatocytes. In the presence of 4 and 5 μM RDV resulted in a significant decrease in hepatocyte viability, up to 50% increase in the proportion of non-viable hepatocytes after 48 hr (P 0.001). Besides, the expression of both ALT and AST significantly increased after treatment with RDV (P 0.001). Our data demonstrated a significant increase in the function of both ALT and AST in the RDV+ group. Conclusion: We concluded that treatment with RDV led to increased expression and function of hepatocyte enzymes in vitro.