Oxidative stress in nonalcoholic steatohepatitis

Akinobu Takaki, Daisuke Uchida, Kazuhide Yamamoto

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a disease with increasing prevalence that is potentially lethal after decades of persistent fat toxicity on the liver and accompanying organs. The pathogenesis for the progression of benign nonalcoholic fatty liver (NAFL) to progressive nonalcoholic steatohepatitis (NASH) is acknowledged as a multiple parallel hit process, including fat deposition, genetic factors, insulin resistance, and oxidative stress. Oxidative stress is one of the main pathogenic factors driving the progression of NAFL to NASH. Excessive accumulation of long chain fatty acids results in activation of the mitochondrial b-oxidation pathway and consequent reactive oxygen species (ROS) production. ROS can mediate oxidative stress responses in hepatocytes, Kupffer cells and hepatic stellate cells (HSCs), resulting in hepatocyte damage as well as proinflammatory and profibrogenic responses. ROS detoxification pathway signaling is often damaged in NAFLD following ROS accumulation. Inactivation of the prooxidant production pathway is presently the primary treatment strategy. However, as oxidative stress is an essential response in living organisms, a new treatment strategy that activates toxic oxidative stress detoxifying pathways while maintaining essential oxidative stress responses is preferred.

Original languageEnglish
Title of host publicationReactive Oxygen Species in Biology and Human Health
PublisherCRC Press
Pages349-361
Number of pages13
ISBN (Electronic)9781498735469
ISBN (Print)9781498735452
DOIs
Publication statusPublished - Jan 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Takaki, A., Uchida, D., & Yamamoto, K. (2017). Oxidative stress in nonalcoholic steatohepatitis. In Reactive Oxygen Species in Biology and Human Health (pp. 349-361). CRC Press. https://doi.org/10.1201/b20228