Effect of cold hypoxic storage and reoxygenation at 37 degrees C of cultured precision-cut rat liver slices on paracetamol metabolism.
The influence of cold storage and reoxygenation at 37 degrees C of precision-cut rat liver slices on paracetamol metabolism was studied. A depressed metabolism was observed after cold preservation, but during reoxygenation at 37 degrees C slices were capable of synthesizing proteins and maintaining both glutathione and ATP levels. Recovery was faster in slices under aerobic cold conditions than in those under cold hypoxia. Glycogen levels were dramatically decreased under both conditions and subsequent reoxygenation at 37 degrees C still increased the glycogenolysis. Xenobiotic metabolism after reoxygenation of cold-preserved slices shows that glucuronide and sulfate conjugates of paracetamol represent about 50% of those of fresh slices at zero time. The amounts of phase II apoproteins were virtually unchanged, thus suggesting that loss of enzyme activities are most probably due to lack of cofactors. Reoxygenation at 37 degrees C did not impair cell metabolism, and a potential role for nitric oxide and other cytokines released form Kupffer cells appears unlikely since nitrite was not formed after bacterial endotoxin stimulation. The maintenance of energetic stores during cold preservation appears, therefore, to be a critical issue for the survival and metabolic activity of cells.
Evdokimova
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Département de Sciences Pharmaceutiques, Université Catholique de Louvain, Brussels, Belgium.
Taper
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Buc Calderon
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D000082:Acetaminophen / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003080:Cold Temperature; D006358:Hot Temperature; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014021:Tissue Preservation
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D000255:Adenosine Triphosphate; D010100:Oxygen