title: Comparative proteomic analysis of 2-MCPD- and 3-MCPD-induced heart toxicity in the rat.
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.
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schultrich
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Frenzel
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Oberemm
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buhrke
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany. Albert.Braeuning@bfr.bund.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Braeuning
authors.affiliation: Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism*; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D017208:Rats, Wistar; D000517:alpha-Chlorohydrin / Q000008:administration & dosage / Q000633:toxicity*; D011409:Propylene Glycols
chemical_list: D005990:Glycerol; D011506:Proteins; D000517:alpha-Chlorohydrin; C585004:monochloropropanediol; D011409:Propylene Glycols
keywords: Cardiotoxicity; Heat-induced food contaminant; MCPD esters; Monochloropropanediol