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

Area of Science:

• Biochemistry
• Pharmacology
• Toxicology

Background:

• Metabolomics offers insights into drug safety and biochemical effects.
• Favipiravir, used for COVID-19, is linked to organ damage, including cardiac issues.
• The specific metabolic impact of favipiravir on heart tissue requires comprehensive analysis.

Purpose of the Study:

• To investigate the metabolic alterations in rat heart tissue induced by favipiravir treatment using metabolomics.
• To assess the dose-dependent effects of favipiravir on cardiac metabolism.
• To elucidate the biochemical mechanisms underlying favipiravir-induced cardiotoxicity.

Main Methods:

• Utilized high-resolution 1H NMR-based metabolomics.
• Employed 60 male Wistar Albino rats divided into control, low-dose (200 mg/kg), and high-dose (300 mg/kg) favipiravir groups.
• Analyzed heart tissue samples collected after oral gavage administration.

Main Results:

• Significant, dose-dependent changes in cardiac metabolites were observed.
• Favipiravir treatment led to decreased ATP, citrate, and valine, with increased lactate and AMP, indicating impaired mitochondrial energy production and a shift to anaerobic glycolysis.
• Higher favipiravir doses resulted in more pronounced disruptions, including reduced glutamate, glutamine, aspartate, tyrosine, 3-methylhistidine, and asparagine, suggesting wider metabolic dysfunction.

Conclusions:

• Favipiravir treatment significantly alters cardiac metabolism in a dose-dependent manner.
• The observed metabolic changes suggest impaired mitochondrial function and energy production, contributing to favipiravir's cardiotoxic effects.
• NMR-based metabolomics is a valuable tool for identifying drug-induced metabolic disturbances and assessing drug safety.