The Effect of Remdesivir as an anti-COVID-۱۹ 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-۱۹ and the impact of COVID-۱۹ 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, ۲۰ embryonated chicken eggs (stage X) were incubated (۳۷.۵ °C, ۶۰-۶۵% humidity) for ۱۰ days (stage HH۳۵). The hepatocytes were cultured in DMEM/F۱۲+۱۰% FBS medium and treated with four concentrations of RDV (۲.۰۰, ۳.۰۰, ۴.۰۰, and ۵.۰۰ 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 ۴ and ۵ μM RDV resulted in a significant decrease in hepatocyte viability, up to ۵۰% increase in the proportion of non-viable hepatocytes after ۴۸ hr (P<۰.۰۰۱). Besides, the expression of both ALT and AST significantly increased after treatment with RDV (P<۰.۰۰۱). 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.

Keywords:

COVID-۱۹ , Remdesivir , Aminotransferases , Hepatocytes , کووید-۱۹ , رمدسیویر , آمینوترانسفرازها , سلول های هپاتوسیتی