The Role and Study of Mitochondrial Impairment and Oxidative Stress in Cholestasis

Methods Mol Biol. 2019;1981:117-132. doi: 10.1007/978-1-4939-9420-5_8.

Abstract

The blockage of bile flow, cholestasis, could lead to serious clinical outcomes, including severe liver injury. Accumulation of the cytotoxic molecules, such as bile acids, during cholestasis, not only impairs liver function, but also affects other organs, including the kidneys. Although the precise mechanisms of cytotoxicity and organ injury in cholestasis are far from clear, oxidative stress and its subsequent events seem to play a central role in this complication. Oxidative stress acts as a signaling path which could finally lead to cell death and organ injury. At the cellular level, mitochondria are major targets affected by cytotoxic molecules. Mitochondrial impairment could lead to severe outcomes, including cellular energy crisis and release of cell death mediators from this organelle. Therefore, targeting oxidative stress and mitochondrial dysfunction might serve as a therapeutic point of intervention against cholestasis-associated organ injury. In this protocol, an animal model of cholestasis is described, and the techniques for liver mitochondria isolation, evaluating mitochondrial indices of functionality, and assessing biomarkers of oxidative stress in the liver tissue are outlined.

Keywords: Apoptosis; Bile acids; Bioenergetics; Cellular energy crisis; Cholestasis; Mitochondria-mediated cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bile Acids and Salts / metabolism
  • Cholestasis / metabolism*
  • Cholestasis / pathology
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Oxidative Stress / physiology

Substances

  • Bile Acids and Salts