Deuterium-Reinforced Polyunsaturated Fatty Acids Prevent Diet-Induced Nonalcoholic Steatohepatitis by Reducing Oxidative Stress.

Abstract

Background and Objectives: Oxidative stress is implicated in the progression of nonalcoholic steatohepatitis (NASH) through the triggering of inflammation. Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species (ROS)-initiated chain reaction of lipid peroxidation than regular hydrogenated (H-) PUFAs. Here, we aimed to investigate the impacts of D-PUFAs on oxidative stress and its protective effect on NASH. Materials and Methods: C57BL/6 mice were randomly divided into three groups and were fed a normal chow diet, a methionine-choline-deficient (MCD) diet, and an MCD with 0.6% D-PUFAs for 5 weeks. The phenotypes of NASH in mice were determined. The levels of oxidative stress were examined both in vivo and in vitro. Results: The treatment with D-PUFAs attenuated the ROS production and enhanced the cell viability in tert-butyl hydroperoxide (TBHP)-loaded hepatocytes. Concurrently, D-PUFAs decreased the TBHP-induced oxidative stress in Raw 264.7 macrophages. Accordingly, D-PUFAs increased the cell viability and attenuated the lipopolysaccharide-stimulated proinflammatory cytokine expression of macrophages. In vivo, the administration of D-PUFAs reduced the phenotypes of NASH in MCD-fed mice. Specifically, D-PUFAs decreased the liver transaminase activity and attenuated the steatosis, inflammation, and fibrosis in the livers of NASH mice. Conclusion: D-PUFAs may be potential therapeutic agents to prevent NASH by broadly reducing oxidative stress.

• Authors: Haoran Li, Ouyang Zhang, Chenmin Hui, Yaxin Huang, Hengrong Shao, Menghui Song, Lingjia Gao, Shengnan Jin, Chunming Ding, Liang Xu
• Journal: Medicina (Kaunas, Lithuania) (Medicina (Kaunas)) Vol. 58 Issue 6 (Jun 12 2022) ISSN: 1648-9144 [Electronic] Switzerland
• PMID: 35744053 (Publication Type: Journal Article)

Chemical References

• Deuterium
• Fatty Acids, Unsaturated
• Methionine
• Reactive Oxygen Species

Topics

• Animals
• Humans
• Mice
• Choline Deficiency (complications, metabolism)
• Deuterium
• Diet
• Disease Models, Animal
• Fatty Acids, Unsaturated (pharmacology)
• Inflammation (drug therapy)
• Liver (metabolism)
• Methionine (pharmacology, therapeutic use)
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (drug therapy, etiology, prevention & control)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)