摘要：

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.

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