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03 July 2018 : Animal Research  

Pathogenesis of Abnormal Hepatic Lipid Metabolism Induced by Chronic Intermittent Hypoxia in Rats and the Therapeutic Effect of N-Acetylcysteine

Haipeng Wang123ABCDEFG, Yan Wang12BDE, Tongliang Xia12CEF, Yaxuan Liu12CF, Ting Liu12CE, Xiaoli Shi12DE, Yanzhong Li42ADEG*

DOI: 10.12659/MSM.907228

Med Sci Monit 2018; 24: ANS4583-4591

Abstract

BACKGROUND: The pathogenesis of chronic intermittent hypoxia (CIH)-induced abnormal hepatic lipid metabolism in rats remains unclear. Here, we investigated the therapeutic effect of N-acetylcysteine (NAC) on abnormal hepatic lipid metabolism.

MATERIAL AND METHODS: Rats were subjected to hypoxia and NAC treatment, and evaluated in terms of hepatic lipid metabolism, hepatocyte ultrastructure, oxidative stress in hepatocytes, expression of nuclear factor-kappa B (NF-κB) and inflammatory cytokines (IL-1β, IL-6, and TNFα), serum lipoprotein lipase (LPL) levels, and blood lipids (triglycerides and cholesterol).

RESULTS: Compared to the normoxic control group, animals in the hypoxic model group showed significant body weight gain; abnormal hepatic lipid metabolism; lipid vacuolization; accumulation of lipid droplets; abundant autophagosomes and lysosomes; significant increases in oxidative stress, inflammation level, and blood lipid levels; and significantly reduced LPL levels. Compared to control animals, rats in the treatment group exhibited normal body weight gain, improved lipid metabolism, fewer lipid droplets, alleviated ultrastructural injuries, decreased oxidative stress and inflammation level, as well as elevated LPL and reduced blood lipid levels.

CONCLUSIONS: The harmful effects of CIH on rat liver are possibly associated with the reactive oxygen species (ROS)/NF-κB signaling pathway. NAC is capable of attenuating lipid metabolism alterations and abnormal body weight gain in the CIH rat model, via a possible mechanism related to inhibition of ROS/NF-κB signaling.

Keywords: Acetylcysteine, Cell Hypoxia, Lipid Metabolism, Oxidative Stress

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750