INCREASED PLASMA LEVELS OF THE LIPOPEROXYL RADICAL-DERIVED VITAMIN E METABOLITE Α-TOCOPHERYL QUINONE ARE AN EARLY INDICATOR OF LIPOTOXICITY IN FATTY LIVER SUBJECTS

Authors    Torquato P, Bartolini D, Giusepponi D, Piroddi M, Sebastiani B, Saluti G, Galarini R, Galli F

Abstract    Lipid peroxidation is one of the earliest pathogenic events of non-alcoholic fatty liver disease (NAFLD). In this context, an increased oxidation of the lipoperoxyl radical scavenger α-tocopherol (α-TOH) should occur already in the subclinical phases of the disease to compensate for the increase oxidation of the lipid excess of liver and possibly of other tissues. However, this assumption remains unsupported by direct analytical evidence. In this study, GC-MS/MS and LC-MS/MS procedures have been developed and applied for the first time to measure the vitamin E oxidation metabolite α-tocopheryl quinone (α-TQ) in plasma of fatty liver (FL) subjects that were compared in a pilot cross-sectional study with healthy controls. The protein adducts of 4-hydroxynonenal (4-HNE) and the free form of polyunsaturated free fatty acids (PUFA) were measured as surrogate indicators of lipid peroxidation. α-TQ formation was also investigated in human liver cells after supplementation with α-TOH and/or fatty acids (to induce steatosis). Compared with controls, FL subjects showed increased (absolute and α-TOH-corrected) levels of plasma α-TQ and 4-HNE, and decreased concentrations of PUFA. α-TQ levels positively correlated with indices of liver damage and metabolic dysfunction, such as alanine aminotransferase, bilirubin and triglycerides, and negatively correlated with HDL cholesterol. Fatty acid supplementation in human hepatocytes stimulated the generation of cellular oxidants and α-TOH uptake leading to increased α-TQ formation and secretion in the extracellular medium - both were markedly stimulated by α-TOH supplementation. In conclusion, plasma α-TQ represents an early biomarker of the lipoperoxyl radical-induced oxidation of vitamin E and lipotoxicity of the fatty liver.

Publish Date   2019

Volume   131

ISSN   1873-4596

DOI  doi.org/10.1016/j.freeradbiomed.2018.11.036

URL    https://www.sciencedirect.com/science/article/pii/S0891584918317477?via%3Dihub

Journal    Free Radical Biology and Medicine

Pages     115-125

PMID  30508576