Toxicity of antiviral Remdesivir on human liver’s ATP binding cassette subfamily D member 3 transporters
DOI:
https://doi.org/10.15218/zjms.2024.24Keywords:
Remdesivir, Covid-19, Hepatotoxicity, Cell transporters, ExpressionAbstract
Background and objective: The World Health Organization advises against the use of the antiviral drug Remdesivir to treat severe COVID-19 infections due to potential toxicity. The molecular mechanism of this toxicity is not well established. ATP-binding cassette (ABC) transporters play an essential role in the transport of various drugs in many illnesses.
Objective: This study examines the possible role of ATP-binding cassette, subfamily D, member 3 (ABCD3) in Remdesivir toxicity.
Methods: Real-time PCR and MTT assays were used to demonstrate the toxicity of Remdesivir on ABCD3 gene expression in the HepG2 cell line. Enzyme-linked immunosorbent assay was used to detect serum ABCD3 levels, Prestige24i was used to detect C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum. Nano-Checker710 was used to detect D-dimer in the serum of the patients.
Results: Remdesivir exhibits dose-dependent toxicity to the HepG2 cell line. The drug toxicity is significantly increased at three doses of 5, 10, and 20 µg/ml in virus-free hepatic cell lines. It suppressed ABCD3 gene expression in both the HepG2 cell line and COVID-19 patients’ sera. COVID-19 virus increases serum levels of CRP, ALT, AST and D-dimer. The drug lowers serum CRP, transiently lowers D-dimer, and increases ALT and AST levels.
Conclusion: Remdesivir suppressed ABCD3 gene expression and increased levels of inflammatory markers. Remdesivir contributes to hepatocyte damage independently of the COVID-19 virus.
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References
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