Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice

The toxic effects of alcohol consumption on population health are significant worldwide and the synergistic toxic effects of concurrent intake of Acetaminophen and alcohol is of clinical concern. The understanding of molecular mechanisms beneath such synergism and acute toxicity may be enhanced through assessing underlying metabolomics changes. The molecular toxic activities of the model hereby, is assessed though metabolomics profile with a view to identifying metabolomics targets which could aid in the management of drug-alcohol interactions. In vivo exposure of C57/BL6 mice to APAP (70 mg/kg), single dose of ethanol (6 g/kg of 40%) and APAP after alcohol consumption was employed. Plasma samples were prepared and subjected to biphasic extraction for complete LC-MS profiling, and tandem mass MS2 analysis. Among the detected ions, 174 ions had significant (VIP scores >1 and FDR <0.05) changes between groups and were selected as potential biomarkers and significant variables. The presented metabolomics approach highlighted several affected metabolic path-ways, including nucleotide and amino acid metabolism; aminoacyl-tRNA biosynthesis as well as bioenergetics of TCA and Krebs cycle. The impact of APAP on the concurrent administration of alcohol showed great biological interactions in the vital ATP and amino acid producing processes. The metabolomics changes show distinct metabolites which are altered to alcohol-APAP consumption while presenting several unneglectable risks on the vitality of metabolites and cellular molecules which shall be concerned.

Automated summary

Alcohol consumption has significant toxic effects on population health worldwide, and the concurrent intake of Acetaminophen and alcohol is a concern in clinical settings. Understanding the molecular mechanisms behind this synergistic toxicity and acute effects can be improved through analyzing metabolomics changes. This study assessed the molecular toxic activities using metabolomics profiling to identify potential biomarkers and significant variables that could aid in managing drug-alcohol interactions.