Assessing the impact of antiviral drugs commonly utilized during the COVID-19 pandemic on the embryonic development of Xenopus laevis

• Published in: Journal of hazardous materials 2024-07, Vol.472, p.134462-134462, Article 134462
• Main Authors: Laçin, Cemal, Turhan, Duygu Ozhan, Güngördü, Abbas
• Format: Article
• Language: English
• Subjects: Amides - toxicity; Animals; Antiviral Agents - toxicity; Antiviral drugs; Biomarkers COVID-19; Carboxylesterase - metabolism; COVID-19; COVID-19 Drug Treatment; Embryo, Nonmammalian - drug effects; Embryonic Development - drug effects; Larva - drug effects; Oseltamivir - toxicity; Pyrazines - toxicity; SARS-CoV-2 - drug effects; Teratogens - toxicity; Toxicity; Xenopus laevis
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.134462

The antiviral drugs favipiravir and oseltamivir are widely used to treat viral infections, including coronavirus 2019 (COVID-19), and their levels are expected to increase in the aquatic environment. In this study, the potential toxic and teratogenic effects of these drugs were evaluated using the frog embryo teratogenesis assay Xenopus (FETAX). In addition, glutathione S-transferase (GST), glutathione reductase (GR), catalase, carboxylesterase (CaE), and acetylcholinesterase (AChE) enzyme activities and malondialdehyde levels were measured as biochemical markers in embryos and tadpoles for comparative assessment of the sublethal effects of the test compounds. Prior to embryo exposure, drug concentrations in the exposure medium were measured with high-performance liquid chromatography. The 96-h median lethal concentration (LC50) was 137.9 and 32.3 mg/L for favipiravir and oseltamivir, respectively. The teratogenic index for favipiravir was 4.67. Both favipiravir and oseltamivir inhibited GR, CaE, and AChE activities in embryos, while favipiravir increased the GST and CaE activities in tadpoles. In conclusion, favipiravir, for which teratogenicity data are available in mammalian test organisms and human teratogenicity is controversial, inhibited Xenopus laevis embryo development and was teratogenic. In addition, sublethal concentrations of both drugs altered the biochemical responses in embryos and tadpoles, with differences between the developmental stages. [Display omitted] •Toxicity of commercial and pure forms of the tested drugs was found similar.•Favipiravir inhibits the development of X. laevis embryos and is teratogenic.•Sublethal concentrations of both drugs caused enzyme inhibition in embryos.•Sublethal concentrations of favipiravir induced deoxification enzymes in tadpoles.•Enzyme activities differed in embryos and tadpoles exposed to the drugs.