Bioactive lipids are altered in the heart, kidney, and serum of male and female F344 rats sub-chronically exposed to dietary 2-MCPD.

Chloropropanols have been identified as processing-induced food contaminants that occur as by-products of the manufacturing of refined food oils and hydrolyzed vegetable protein. There has been a paucity of research on the 2-monochloropropane-1,3-diol (2-MCPD) isomer, thus forming a data gap for regulatory risk assessment. Previous studies suggest 2-MCPD causes adverse cardiotoxic, nephrotoxic, and myotoxic effects, but were inconclusive for hazard identification; thus a dose-response OECD TG-408-compliant study was conducted by Health Canada. Our study profiled the effects of 2-MCPD on oxylipins and oxidized phosphatidylcholines, using HPLC-MS/MS, in heart, kidney, serum, and skeletal muscle of male and female F344 rats orally exposed to 2-MCPD (40 mg/kg BW/d) for 90 days. Cardiac n-3 polyunsaturated fatty acid-derived oxylipins, particularly DHA-derived oxylipins, were lower with 2-MCPD exposure, coincident with cardiac lesions. Lipoxygenase-derived oxylipins were decreased in the serum with a greater effect in the male 2-MCPD treatment group. Few oxylipin alterations were seen in the kidney and there was an absence of alterations in the tibialis anterior. Oxidized phosphatidylcholines and isoprostanes were not altered in this study, indicating that oxidative stress was not elevated by 2-MCPD. These findings add to the weight of the evidence for 2-MCPD toxicity and support the use of serum oxylipins as potential biomarkers of 2-MCPD exposure.

Cayer LGJ ，Roberts J ，Raju J ，Aukema HM ... -  《-》

An integrated multi-omics analysis of the effects of the food processing-induced contaminant 2-monochloropropane-1,3-diol (2-MCPD) in rat heart.

Cayer LGJ ，Buhrke T ，Roberts J ，Nunnikhoven A ，Sommerkorn K ，Reinhold A ，Braeuning A ，Raju J ，Aukema HM ，Karakach T ... -  《-》

Cardiac oxylipin perturbances in response to 2-monochloropropane-1,3-diol exposure are ameliorated by dietary adequacy of the essential n-3 fatty acid, α-linolenic acid.

2-Monochloropropane-1,3-diol (2-MCPD) is a food contaminant with demonstrated cardiotoxicity in rats. This adverse effect was previously associated with lower anti-inflammatory docosahexaenoic acid (DHA)-derived cardiac oxylipins in F344 rats. This previous study utilized corn oil as the dietary lipid; we therefore investigated whether deficient (0.07 g/100 g diet) or adequate (0.5 g/100 g diet) dietary α-linolenic acid (ALA), the essential n-3 polyunsaturated fatty acid (PUFA), alters the oxylipin response in heart, liver, kidney, and serum of Sprague-Dawley rats exposed to 50 mg 2-MCPD/kg BW/day. ALA increased n-3 oxylipins in all tissues, reflecting greater n-3 PUFA substrate availability. In the heart, 2-MCPD increased cyclooxygenase-derived arachidonic acid oxylipins, conducive to inflammation. Adequate dietary ALA revealed 2-MCPD-induced reductions of anti-inflammatory cardiac DHA-derived oxylipins; these were not apparent in the ALA-deficient diet as these n-3 PUFA oxylipins were already reduced. Conversely, 2-MCPD increased cardiac 13-hydroxy-octadecatrienoic acid-γ (13-HOTrE-γ) levels with deficient, but not adequate, ALA diets. Multi-tissue analysis identified 13-HOTrE-γ as a marker of 2-MCPD exposure. Our study contributes to the weight-of-evidence of 2-MCPD toxicity, confirms the functional and indicative roles of oxylipins in the heart, and demonstrates that live bioassays determining chemical health hazards should use adequate n-3 PUFA diets.

Cayer LG ，Karakach T ，Roberts J ，Brooks SP ，Raju J ，Aukema HM ... -  《-》

Effects of subacute 3-monochloropropane-1,2-diol treatment on the kidney of male albino rats.

Mahmoud YI ，Abo-Zied FS ，Salem ST 《-》

A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

Onami S ，Cho YM ，Toyoda T ，Mizuta Y ，Yoshida M ，Nishikawa A ，Ogawa K ... -  《-》