2-MCPD-Induced Effects in the Heart: Toxicological and Mechanistic Implications from Comparative Proteomic Analyses...

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in a subchronic (90 days, in 2024) oral toxicity rat study. Here, we set out to perform an updated analysis and re-evaluation of these proteomic in vivo data in a comparative manner and in the context of 2-MCPD metabolism, focusing in particular on mitochondrial energy metabolism and the maintenance of the structural integrity and function of the heart. The aim of our project was to develop further reasonable, toxicologically relevant research hypotheses for future studies addressing this topic in order to shed more light on the-so far-rather limited knowledge of the toxicological properties and modes of action of 2-MCPD. Our updated data analysis and comparative re-evaluation revealed strong indications of cytoskeletal protein deregulation, indicative of cardiomyocyte degeneration, and the deregulation of enzyme proteoforms linked to carbohydrate utilization and mitochondrial functions. This led us to hypothesize that reactive metabolites of 2-MCPD, other than those formed from 3-MCPD, could impair mitochondrial pyruvate utilization and mitochondrial energy production, potentially resulting in cardiac functional heart failure in rats at doses slightly higher than 10 mg 2-MCPD per kg bw/day. Thus, we postulate the intermediate formation of some putative aldehydic and acidic metabolites following oral 2-MCPD exposure that might be causative of cardiotoxicity in rats.