Effects of exposure to benzo[a]pyrene and chronic stress on hepatic metabolism of mice
Environmental pollutants and chronic stress are two common risk factors that have great impact on human health.In this study,potential interactions between these two factors were explored by characterizing the effects of benzo[a]pyrene(B[a]P),or chronic stress,or their combination,on liver metabolism of male C57BL/6J mice using targeted metabolomics followed by multivariate statistical analysis.It was found that the hepatic levels of alanine and glutamine were significantly up-and down-regulated respectively after 21 days of exposure to 2.0 mg·kg-1·d-1 or 20.0 mg·kg-1·d-1 of B[a]P.But only in the 2.0 mg·kg1·d-1 case did we observe the up-regulation of argininosuccinic acid and arginine,suggesting that the B[a]P-induced alterations in amino acid metabolism were dose dependent.Moreover,chronic stress stimulus was found associated with a significant decrease in the hepatic level of homocysteine.Also,we evaluated the effects of combined exposure on the hepatic metabolism based on the metabolic effect level index(MELI).Specifically,the combined exposure to 2.0 mg·kg-1·d-1 B[a]P and chronic stress exhibited antagonistic,synergistic and additive effects on amino acid metabolism,TCA cycle and bile acid metabolism,respectively.In contrast,the combined exposure to 20.0 mg·kg 1 d-1 B[a]P and chronic stress showed additive effects on both amino acid metabolism and bile acid metabolism,but antagonistic effect on TCA cycle.We conclude that the exposure to both B[a]P and chronic stress can trigger significant disorders in amino acid and bile acid metabolism,which,notably,differ from those caused by exposure to either alone and were closely related to the exposure dose of B[a]P.
万方数据
维普
