Prolonged PM2.5 exposure elevates risk of oxidative stress-driven nonalcoholic fatty liver disease by triggering increase of dyslipidemia

Free Radic Biol Med. 2019 Jan;130:542-556. doi: 10.1016/j.freeradbiomed.2018.11.016. Epub 2018 Nov 19.

Abstract

An increasing number of studies have shown that air pollution containing particulate matter (PM) ≤ 2.5 µm (PM2.5) plays a significant role in the development of metabolic disorder and other chronic diseases. Inflammation and oxidative stress caused by metabolic syndrome are widely determined to be critical factors in the development of nonalcoholic fatty liver disease (NAFLD) pathogenesis. However, there is no direct evidence of this, and the underlying molecular mechanism is still not fully understood. In this study, we investigated the role of inflammation and oxidative stress caused by prolonged PM2.5 exposure in dyslipidemia-associated chronic hepatic injury, and further determined whether an increase in hepatic inflammation and oxidative stress promoted lipid accumulation in the liver, ultimately increasing the risk of NAFLD. Therefore, we studied changes in indicators of metabolic disorder and in symbolic indices of NAFLD. We confirmed increases in insulin resistance, glucose tolerance, peripheral inflammation and dysarteriotony in PM2.5-induced mice. Oxidative stress and inflammatory response in the liver caused by PM2.5 inhalation contributed to abnormal hepatic function, further promoting lipid accumulation in the liver. Moreover, we observed inhibition of oxidative stress and inflammatory response by pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) in vitro, suggesting that oxidative stress and inflammatory in liver cells aggravated by PM2.5 contributed to hepatic injury by altering normal lipid metabolism. These results indicate a new goal for preventing and treating air pollution-induced diseases: suppression of oxidative stress and inflammatory response.

Keywords: Chronic liver injury; Dyslipidemia; Lipid accumulation; Nonalcoholic fatty liver disease (NAFLD); Particular matter 2.5 (PM2.5).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Air Pollutants / toxicity
  • Animals
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Dyslipidemias / pathology
  • Hepatocytes / drug effects
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin Resistance / genetics
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Oxidative Stress / drug effects*
  • Particulate Matter / chemistry
  • Particulate Matter / toxicity*
  • Pyrrolidines / pharmacology
  • Signal Transduction / drug effects
  • Thiocarbamates / pharmacology

Substances

  • Air Pollutants
  • Particulate Matter
  • Pyrrolidines
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid
  • Acetylcysteine