Metabolomics is a powerful tool for assessing drug safety and understanding the biochemical effects of pharmaceutical compounds. Favipiravir, a drug widely used during the COVID-19 pandemic, has been associated with damage to various organs, including the heart. However, a comprehensive analysis of its metabolic impact on cardiac tissue has not yet been performed. This study utilized high-resolution 1H NMR-based metabolomics to investigate metabolic alterations in rat heart tissue following favipiravir treatment. For this purpose, 60 male Wistar Albino rats were randomly assigned to three groups: control, low-dose favipiravir (200 mg/kg), and high-dose favipiravir (300 mg/kg), with 20 rats in each group. Treatments were administered via oral gavage, and heart tissue samples were collected for 1H NMR analysis after the treatment period. Bioinformatics analysis results showed significant dose-dependent changes in key metabolites in the favipiravir-treated groups. Decreased levels of ATP, citrate, and valine accompanied by increased levels of lactate and AMP suggest a disruption in mitochondrial energy production and a shift towards anaerobic glycolysis. At the higher dose, more pronounced disruptions were noted, including decreases in glutamate, glutamine, aspartate, tyrosine, 3-methylhistidine, and asparagine, suggesting a broader metabolic dysfunction. These findings offer valuable insights into the cardiotoxic effects of favipiravir and highlight the utility of NMR metabolomics in identifying drug-induced metabolic disturbances.
Keywords: COVID‐19; NMR spectroscopy; favipiravir; heart; metabolomics.
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