Glucose transport and hypoxia-reoxygenation injury in the perfused rat liver.
During liver transplantation, oxidative stress occurs during hypoxia and reoxygenation of the donor organ. Chemical oxidative stress impairs cell membrane transport. Therefore, in this study the influence of hypoxia and reoxygenation on hepatocellular membrane transport was investigated. Specifically, glucose transport was studied in the perfused rat liver using the multiple indicator-dilution technique. First, it was observed that in normal rat livers, glucose transport was rapid but saturable (Km 48 +/- 10 mmol/L and Vmax 9.4 +/- 0.9 mumol/s per g of liver). To stimulate hypoxia and reoxygenation, livers were perfused for 30 min with nitrogen-saturated buffer and then with oxygen-saturated buffer for 20 min. The livers from fed rats were protected from hypoxia-reoxygenation injury whereas those from fasted rats were highly susceptible to injury as determined by lactate dehydrogenase release. After reoxygenation, the rate of glucose influx decreased significantly by approximately 50% in the fasted livers (P < 0.001) but was unaffected in the fed livers. This impairment of the hepatocellular transport of glucose, which could be secondary to oxidative injury to the hepatocyte membrane, has implications for the function of donor livers that have sustained hypoxia-reoxygenation ('preservation') injury during transplantation.
Le Couteur
D G
DG
University of Queensland Department of Medicine, Brisbane, Australia.
Rivory
L P
LP
Pond
S M
SM
D000818:Animals; D001693:Biological Transport, Active; D015687:Cell Hypoxia; D005215:Fasting / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007201:Indicator Dilution Techniques; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009752:Nutritional Status; D018384:Oxidative Stress; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*
D005947:Glucose