The effect of acute oxidative stress on the ultrastructure of the perfused rat liver

Pharmacol Toxicol. 2001 Dec;89(6):306-11. doi: 10.1034/j.1600-0773.2001.d01-165.x.


Ageing and liver disease are associated with ultrastructural changes in the hepatic sinusoid. Because of the possibility that reactive oxygen species could mediate these processes, we examined the effect of acute oxidative stress on the ultrastructure of the intact liver. Rat livers were perfused ex vivo, in situ with hydrogen peroxide via the portal vein. The livers were then fixed and the ultrastructure of the liver tissue examined with transmission and scanning electron microscopy. The effects of hydrogen peroxide were largely confined to the perisinusoidal areas. The sinusoidal endothelial cells became swollen and more porous, with large gaps replacing sieve plates. The space of Disse showed an increase in volume and the density of hepatocyte projections decreased. Kupffer cell activation was noted. Little or no ultrastructural change was observed within the hepatocytes. Oxidative stress delivered via the portal vein dramatically alters the ultrastructure of the perisinusoidal regions of the liver. This process may contribute to the pathogenesis of disease and age-related changes in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Endothelium / drug effects
  • Hydrogen Peroxide / toxicity
  • Kupffer Cells / drug effects
  • Liver / drug effects
  • Liver / ultrastructure*
  • Male
  • Microscopy, Electron
  • Microscopy, Electron, Scanning
  • Oxidative Stress / physiology*
  • Perfusion
  • Rats
  • Rats, Wistar


  • Hydrogen Peroxide