Lysosomal changes associated with hyperoxia in the isolated perfused rat liver

Abstract

Changes in lysosomes associated with hyperoxia were studied in the isolated rat liver, perfused by the method of Mayes and Felts (1966). Increased PO2 in perfused blood resulted in the formation of enlarged lysosomes and autophagic vacuoles. Demonstration of acid phosphatase (both by light and electron microscopy), β-glucuronidase, aryl sulfatase, and E600-resistant esterase in these organelles identified them as lysosomes. Electron-microscopic observations show that except for changes in the lysosomes, none of the other cellular organelles are distinctly affected. The formation of autophagic vacuoles and the cell damage are prevented if perfusion is carried out with blood oxygenated with air or if the liver is derived from a rat treated with chloroquine. These findings are attributed to alteration in the permeability of the lysosomal membrane resulting from hyperoxia. In turn, this permeability change releases hydrolytic enzymes into the cytoplasm leading to cell death, particularly in the centrilobular areas of the liver in fed and fasted rats. A special role in this process is envisaged for the smaller pericanalicular lysosomes, as indicated by a reduction in their number and a change in their distribution.