V.L. is research assistant of the National Fund for Scientific Research (Belgium).
Fructose metabolism and cell survival in freshly isolated rat hepatocytes incubated under hypoxic conditions: Proposals for potential clinical use
Article first published online: 12 DEC 2005
Copyright © 1994 American Association for the Study of Liver Diseases
Volume 20, Issue 6, pages 1567–1576, December 1994
How to Cite
Lefebvre, V., Goffin, I. and Buc-Calderon, P. (1994), Fructose metabolism and cell survival in freshly isolated rat hepatocytes incubated under hypoxic conditions: Proposals for potential clinical use. Hepatology, 20: 1567–1576. doi: 10.1002/hep.1840200628
- Issue published online: 12 DEC 2005
- Article first published online: 12 DEC 2005
- Manuscript Accepted: 15 JUN 1994
- Manuscript Received: 31 AUG 1993
- Fund of Medical Scientific Research (Belgium). Grant Number: 3.4528.91
The protective effect of fructose with regard to hypoxia-induced cell injury was investigated. The addition of fructose (2 to 20 mmol/L) protected hepatocytes against hypoxia-mediated cell lysis in a concentration-dependent way. The intracellular ATP content was initially decreased as a result of fructose-1-phosphate formation, but it remained constant during the hypoxic incubation. Conversely, high initial ATP values observed at low fructose concentrations progressively declined. Cellular protection was observed only when fructose was added before (and not after) the start of hypoxia. In addition, a sufficient amount of fructose-1-phosphate rapidly accumulated before the induction of hypoxia, and the linear production of lactate, during hypoxic incubation, indicated that cells synthesized ATP continuously. The lack of cell protection by fructose added after the onset of the hypoxia may be explained by a lesser fructose-1-phosphate formation and a subsequently low accumulation leading to insufficient glycolytic ATP production. Under aerobic conditions, both glycolysis (lactate formation) and gluconeogenesis (glucose formation) were carried out in fructose-1-phosphate-loaded cells with the same initial rates, whereas under hypoxic conditions glycolysis was the main metabolic event. The fact that protein synthesis activity recovered faster during reoxygenation of previously hypoxic fructose-treated cells than in glucose-treated cells led us to hypothesize that in situ perfusion of liver with fructose, before its removal, would improve its metabolic capacity during the hypoxic cold preservation and subsequent transplantation. (Hepatology 1994;20:1567–1576).