Phosphatidylcholine protects against the hepatotoxicity of acrylamide via maintaining metabolic homeostasis of glutathione and glycerophospholipid

Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity. Phosphatidylcholine is thought to protect the liver from damage, but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear. We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches. Overall, 32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection. Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione, cysteine and L-ascorbic acid, and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation. The phosphatidylcholine treatment reduces the expression of cytochrome P450 2E1, alleviates the oxidative stress and inflammation of the liver, and stabilizes the content of glutathione, and thus alleviates the disorder of glutathione. Meanwhile, phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol, thereby maintaining metabolic homeostasis of glycerophospholipid. The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure, but not significantly change the levels of mercapturic acid adducts of acrylamide, providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.