Deleterious effects of xanthine oxidase on rat liver endothelial cells after ischemia/reperfusion

AbstractPrevious studies have demonstrated that reactive oxygen species are involved in ischemic injury. The present work was undertaken to determine in vivo the role of xanthine oxidase in the oxygen free radical production during rat liver ischemia and to examine the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) during the same period. Our results indicate a 4-fold increase in xanthine oxidase activity between 2 and 3 hours of normothermic ischemia, in parallel with a decrease in cell viability. Moderate hypothermia delays both events. Under the same conditions, the activity of oxygen radical scavenging enzymes remains unchanged. Moreover, we have compared in vitro the susceptibility of isolated liver cells to an oxidative stress induced by O2·−, H2O2 and OH. Our results reveal that endothelial cells are much more susceptible to reactive oxygen species than hepatocytes, probably because they lack H2O2-detoxifying enzymes. These findings suggest that xanthine oxidase might play a major role in the ischemic injury mainly at the level of the sinusoidal space where most endothelial cells are located

Biological functions of lysosomal membrane-associated glycoproteins

Lysosomes are the final repository of degradation products from the extracellular and intracellular spaces. The lysosomal membrane forms a unique vacuole participating in both endocytosis and autophagocytosis. It is extremely resistant to degradation by lysosomal hydrolases, maintains an acidic intralysosomal environment, transports amino acids and oligosaccharides produced by lysosomal hydrolases, interacts and fuses with other membrane organelles, such as endosomes and phagosomes, and with the plasma membrane.Biomedical Reviews 1997; 8: 119-125

Diethanolamine-induced alteration of hepatic mitochondrial function and structure

Diethanolamine (DEA) has been shown to interfere with phospholipid metabolism. It was hypothesized that DEA may alter membrane-bound biochemical processes which are dependent upon phospholipids. DEA was investigated for its effect on hepatic mitochondrial function and structure in the male Sprague-Dawley rat. DEA did not produce mitochondrial alterations in in vitro preparations from liver tissue. Similarly, acute treatment in vivo was without effect. However, a loss of mitochondrial integrity developed after subacute administration of DEA. Rats were given 0.25 (42 mg/kg/day), 1.0 (160 mg/kg/day), or 3.0 (490 mg/kg/day) mg/ml in their drinking water for varying periods up to 5 weeks. The effects on mitochondria were dose- and time dependent. Significant alterations appeared after 3 days at 3.0 mg/ml and after 1 week at 1.0 mg/ml. Mitochondrial State 4 activity was significantly elevated at all three dose levels following 2 weeks of DEA treatment. Concomitantly, an increase was noted in the Mg2+-dependent ATPase activity from rats treated with DEA at 2.0 mg/ml for 3 weeks. Electron micrographs indicated that treated animals had swollen hepatic mitochondria. The changes in the organelle may be related to alteration of phospholipid metabolism by DEA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23610/1/0000572.pd

The permeability of lysosomes to sugars. Effect of diethylstilbestrol on the osmotic activation of lysosomes induced by glucose

We have investigated the effect on the osmotic activation of rat liver lysosomes, by glucose penetration, of different substances known to inhibit the glucose transport through the plasma membrane. Diethylstilbestrol is the most efficient, particularly when purified lysosomes are used. It has no effect on osmotic activation induced by hypo-osmotic sucrose or by iso-osmotic KCl. It is proposed that diethylstilbestrol reacts with specific sites involved in the glucose translocation through the lysosomal membrane. These sites could not be identified by binding experiments, presumably owing to the considerable unspecific binding of the compound to the membrane

Effects of wine on cellular and endocellular membranes <em>in vitro</em>

Several observations suggest that wine consumption could have beneficial effects on health by preventing cardiovascular diseases. Apparently, ethanol is not the only component responsible for these effects, phenolic substances: tanins, flavonoids may have an important role. As these compounds are able to affect biological membranes, we investigated the effect of wine in vitro on two model membranes: the lysosomal membrane and the red cell membrane. The integrity of rat liver lysosomal membrane was assessed by measuring the latency of Nacetylglucosaminidase, a lysosomal enzyme, when the organelles are subjected to free radicals of oxygen in the presence of different concentrations of wine. The state of red cell membrane was followed by determining hemolysis caused by phospholipase C. Our results show that low concentrations of red wine prevent the deterioration of the membrane of lysosomes induced by oxygen free radicals generated by the xanthine-xanthine oxidase system and oppose hemolysis induced by treating red cells with Clostridium welchii phospholipase C. White wine is considerably less efficient. As similar effects can be obtained with some phenolic compounds, it is probable that the membrane protective effects of red wine that we describe, originate from its content in these substances