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Comparative proteomic analysis of 2-MCPD- and 3-MCPD-induced heart toxicity in the rat

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Abstract

The chlorinated propanols 2- and 3-monochloropropanediol (MCPD), and their fatty acid esters have gained public attention due to their frequent occurrence as heat-induced food contaminants. Toxic properties of 3-MCPD in kidney and testis have extensively been characterized. Other 3-MCPD target organs include heart and liver, while 2-MCPD toxicity has been observed in striated muscle, heart, kidney, and liver. Inhibition of glycolysis appears to be important in 3-MCPD toxicity, whereas mechanisms of 2-MCPD toxicity are still unknown. It is thus not clear whether toxicity by the two isomeric compounds is dependent on similar or dissimilar modes of action. A 28-day oral feeding study in rats was conducted using daily non-toxic doses of 2-MCPD or 3-MCPD [10 mg/kg body weight], or an equimolar (53 mg/kg body weight) or a lower (13.3 mg/kg body weight) dose of 2-MCPD dipalmitate. Comprehensive comparative proteomic analyses of substance-induced alterations in the common target organ heart revealed striking similarities between effects induced by 2-MCPD and its dipalmitate ester, whereas the degree of effect overlap between 2-MCPD and 3-MCPD was much less. The present data demonstrate that even if exerting effects in the same organ and targeting similar metabolic networks, profound differences between molecular effects of 2-MCPD and 3-MCPD exist thus warranting the necessity of separate risk assessment for the two substances. This study for the first time provides molecular insight into molecular details of 2-MCPD toxicity. Furthermore, for the first time, molecular data on 3-MCPD toxicity in the heart are presented.

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Acknowledgements

Technical assistance by Linda Brandenburger, Christine Meckert and Christel Rozycki is greatly acknowledged. This study was supported by the Federal Institute for Risk Assessment [Grant 1322-542].

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Correspondence to Albert Braeuning.

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Schultrich, K., Frenzel, F., Oberemm, A. et al. Comparative proteomic analysis of 2-MCPD- and 3-MCPD-induced heart toxicity in the rat. Arch Toxicol 91, 3145–3155 (2017). https://doi.org/10.1007/s00204-016-1927-0

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  • DOI: https://doi.org/10.1007/s00204-016-1927-0

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