An LC–MS-based lipidomics approach for studying the impact of dietary eicosapentaenoic acid on modulating methylmercury toxicity in mice

Introduction: Methylmercury (MeHg) exposure has been a public health problem for many decades. There is a growing interest in searching for possible dietary nutrients that may affect MeHg toxicity. Objectives: The study aims to evaluate the impact of eicosapentaenoic acid (EPA) on modulating MeHg toxicity in mice. Methods: The study was based on a two-level factorial design, where the factors were presence or absence of EPA and MeHg in the feed. A liquid chromatography-mass spectrometry-based lipidomics approach was used to identify and quantify the main phospholipid species in mouse liver and plasma. The effects of EPA and MeHg on phospholipid species were evaluated by principal component analysis and statistics. Some biochemical and toxicological markers were measured and hepatic histological assay was carried out. Results: EPA treatment significantly elevated the phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) species that contain n-3 PUFA, and reduced the levels of PtdCho and PtdEtn species that contain arachidonic acid (ARA), while MeHg exhibited opposite effects on these specific PtdCho species in liver. MeHg induced higher prostaglandin E₂ and lower prostaglandin E₃, thus increasing pro-inflammatory factors, while EPA decreased these ARA-derived inflammatory factors. Moreover, MeHg induced chronic inflammatory symptoms in mice, including severe hepatic necrosis, higher aspartate aminotransferase and alanine aminotransferase activities in plasma, higher thiobarbituric acid reactive substances and lower glutathione in liver. These symptoms were all alleviated by EPA treatment. Conclusion: EPA may have protective effect against MeHg-induced toxicity due to the favorable modification of membrane phospholipid composition and inhibition of inflammatory factors.