Hydrogen influences HDL-associated enzymes and reduces oxidized phospholipids levels in rats fed with a high-fat diet

Life Sci. 2021 Feb 15:267:118945. doi: 10.1016/j.lfs.2020.118945. Epub 2020 Dec 29.

Abstract

Aims: Oxidized phospholipids (OxPLs) are formed as a result of oxidative stress, which potentially mediate multiple pathological effects. We aimed to evaluate the effects of hydrogen (H2) on OxPLs in vivo and the underlying mechanism.

Main methods: Rats were randomly assigned to three groups: control group fed with a chow diet, model group fed with a high-fat diet, and H2-treated group fed with a high-fat diet and treated by 4% H2 inhalation for ten weeks. OxPLs in liver and plasma were analyzed by liquid chromatography-mass spectrometry. High-density lipoprotein (HDL) was separated by ultracentrifugation. A proteomic analysis was performed to reveal the alternation of HDL protein composition and he antioxidant capacity of HDL was tested by low-density lipoprotein oxidation experiment. Furthermore, the activity or expression of HDL-associated enzymes were evaluated.

Key findings: Inhalation of 4% H2 decreased the accumulation of OxPLs in rats. In vitro tests revealed that the different concentrations of H2 did not inhibit the formation of OxPLs mediated by non-enzymatic oxidation. H2 inhalation altered the components and enhanced the anti-oxidative capacity of HDL in rats fed with a high-fat diet. Further experiments showed that H2 significantly regulated the activity of lipoprotein-associated phospholipase A2, paraoxonase-1, and the expression of lecithin:cholesterol acyltransferase.

Significance: Our findings revealed that H2 may reduce the OxPLs levels through its influence on HDL-associated enzymes that can act on OxPLs, suggesting that H2 can be used in alleviating diseases related to lipid peroxidation due to oxidative stress.

Keywords: Antioxidant enzyme; High-density lipoprotein; Hydrogen; Oxidized phospholipids; Proteomics.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Antioxidants / pharmacology
  • Apolipoprotein A-I / metabolism
  • Cholesterol, HDL / drug effects
  • Cholesterol, HDL / metabolism
  • Chromatography, Liquid / methods
  • Diet, High-Fat / adverse effects
  • Hydrogen / metabolism*
  • Hydrogen / pharmacology*
  • Lipid Peroxidation
  • Lipoproteins, HDL / drug effects
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / drug effects
  • Lipoproteins, LDL / metabolism
  • Liver / metabolism
  • Male
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Phospholipids / metabolism*
  • Proteomics / methods
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antioxidants
  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Phospholipids
  • oxidized low density lipoprotein
  • Hydrogen
  • Phosphatidylcholine-Sterol O-Acyltransferase