NMR-Based Metabolomics Profiling Reveals Dose-Dependent Cardiotoxic Effects of Favipiravir in Rats

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.