title: Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate-induced toxicity in rat kidney.
abstract: 3-Chloropropane-1,2-diol (3-MCPD) and its fatty acid esters are formed during thermal treatment of fat-containing foodstuff in the presence of salt. Toxicological studies indicate a carcinogenic potential of 3-MCPD, pointing to the kidney as the main target organ. It is assumed that the toxicological property of 3-MCPD esters is constituted by the release of 3-MCPD during digestion. In a repeated-dose 28-day oral toxicity study using Wistar rats, animals were treated with equimolar doses of either 3-MCPD (10 mg/kg body weight) or 3-MCPD dipalmitate (53 mg/kg body weight). A lower dose of 3-MCPD dipalmitate (13.3 mg/kg body weight) was also applied. No histopathologically visible toxicity was observed in the study. To address molecular mechanisms leading to toxicity of 3-MCPD and its esters, kidney samples were analyzed by a comparative, two-dimensional gel electrophoresis/mass spectrometry proteomic approach. After either 3-MCPD or 3-MCPD dipalmitate treatment, alterations in proteins related to various metabolic pathways, including carbohydrate, amino acid, and fatty acid metabolism, were detected. These findings confirm and complement previous data on the inhibition of glucose metabolism by 3-MCPD. Altogether, broad overlap of 3-MCPD- and 3-MCPD dipalmitate-induced proteomic changes was observed. Further analyses revealed that the observed induction of glutathione S-transferase pi 1 (Gstp1) occurred at the transcriptional level and was not related to nuclear factor (erythroid-derived 2)-like 2 activation. Overall, the results indicate common mechanisms of toxicity for 3-MCPD and its dipalmitate ester. Furthermore, data suggest Gstp1 as a sensitive marker for early 3-MCPD-induced effects in rat kidney.
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Oberemm
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buhrke
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Merschenz
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany. Albert.Braeuning@bfr.bund.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Braeuning
authors.affiliation: Department Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003296:Cooking; D015180:Electrophoresis, Gel, Two-Dimensional; D005506:Food Contamination; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome / Q000187:drug effects; D010168:Palmitates / Q000633:toxicity*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D059551:Toxicity Tests, Subacute; D000517:alpha-Chlorohydrin / Q000633:toxicity*
chemical_list: D010168:Palmitates; D020543:Proteome; D000517:alpha-Chlorohydrin; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat
keywords: 3-Chloropropane-1,2-diol; 3-MCPD fatty acid ester; Glutathione S-transferase pi; Nrf2; Proteomics