Evidence for oxidative/nitrosative stress in the pathogenesis of hepatic encephalopathy

Metab Brain Dis. 2010 Mar;25(1):3-9. doi: 10.1007/s11011-010-9177-y. Epub 2010 Mar 2.


Hepatic encephalopathy (HE) is a serious complication of liver failure. HE manifests as a series of neuropsychiatric and neuromuscular symptoms including personality changes, sleep abnormalities, asterixis and muscle rigidity progressing through stupor to coma. The pathophysiologic basis of HE remains unclear. There is general agreement that ammonia plays a key role. In recent years, it has been suggested that oxidative/nitrosative stress constitutes part of the pathophysiologic cascade in HE. Direct evidence for oxidative/nitrosative stress in the pathogenesis of HE has been demonstrated in experimental animal models of acute or chronic liver failure. However, evidence from studies in HE patients is limited. This review summarizes this evidence for a role of oxidative/nitrosative stress in relation to ammonia toxicity and to the pathogenesis of HE.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Cytokines / metabolism
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Free Radicals / metabolism
  • Hepatic Encephalopathy / etiology*
  • Hepatic Encephalopathy / metabolism*
  • Humans
  • Hyperammonemia / metabolism*
  • Hyperammonemia / physiopathology
  • Liver Failure / complications
  • Liver Failure / metabolism
  • Liver Failure / physiopathology
  • Nitrates / metabolism
  • Nitrosation / physiology
  • Oxidative Stress / physiology*


  • Cytokines
  • Free Radical Scavengers
  • Free Radicals
  • Nitrates