The effect of Remdesivir as an anti-COVID-19 drug on chicken hepatocyte enzymes; an in vitro study

Introduction: There is little evidence of potential hepatotoxicity of Remdesivir (RDV), in vitro. 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. Material 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 liver cells were cultured in DMEM/F12+10% FBS medium. After 3 days, four concentrations of RDV (2.00, 3.00, 4.00, and 5.00 µM) were added to the culture medium. Serum levels of alanine (ALT) and aspartate (AST) aminotransferases were measured by Elisa, and gene expression measured by quantitative real-time PCR (qPCR). Results: Each hepatocyte had a hexagonal structure with a large nucleus and nucleolus. In the PAS staining, the PAS-positive cells with a pink color confirmed the glycogen content of hepatocytes. In the presence of 4 and 5 μM RDV, up to 50% of hepatocytes lose their viability after 48 hr (P<0.001). Besides, the expression of both ALT and AST were significantly increased after treatment with RDV (P<0.001). Our data showed that the function of both ALT and AST was significantly increased in the RDV+ group. Conclusion: We concluded that the expression and function of hepatocyte enzymes were increased following treatment with RDV.