Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12971
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dc.contributor.authorAngus, Peter Wen
dc.contributor.authorMihaly, G Wen
dc.contributor.authorMorgan, Denis Jen
dc.contributor.authorSmallwood, R Aen
dc.date.accessioned2015-05-16T02:44:20Z
dc.date.available2015-05-16T02:44:20Z
dc.date.issued1988-04-01en
dc.identifier.citationBiochemical Pharmacology; 37(7): 1207-12en
dc.identifier.govdoc3355595en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12971en
dc.description.abstractIn isolated hepatocytes the availability of intracellular glucose appears to be a key factor controlling the rate of xenobiotic glucuronidation during hypoxia. This study in the isolated perfused rat liver examines the effect of both a 24-hr fast and removal of glucose (8 mM) from liver perfusate on the elimination of bolus doses of harmol (20 mumol) under normoxic and hypoxic conditions. In the preparations used in these experiments, harmol glucuronide is the major metabolite (greater than 80%) with the remainder being sulphate. During normal oxygenation, in the livers from fed rats, harmol was rapidly eliminated (t1/2 = 4.2 +/- 0.4 min; mean +/- SD, N = 4). Fasting led to a small reduction in harmol elimination rate (t1/2 = 5.6 +/- 0.4 min; P less than 0.025) while removal of glucose from perfusate made no difference in either fed or fasted preparations. In the same livers, a second bolus dose of harmol was given during hypoxia. This produced a modest decline in harmol elimination in fed rats (t1/2 = 7.1 +/- 2.0 min; P less than 0.05). However, in fasted rats there was a striking reduction in harmol elimination (t1/2 = 109.8 +/- 54.0 min; P less than 0.025). The removal of glucose from perfusate made no significant difference to these results (t1/2 = 253 +/- 209 min in fasted preparations, P greater than 0.1). In all preparations, reoxygenation resulted in a rapid recovery of drug elimination. We conclude that nutritional state is important in determining the impact of hypoxia on harmol elimination by the liver. This study suggests that clinically significant reductions in xenobiotic glucuronidation are most likely to occur in poorly nourished or fasted subjects who became hypoxaemic.en
dc.language.isoenen
dc.subject.otherAlkaloids.metabolismen
dc.subject.otherAnimalsen
dc.subject.otherAnoxia.metabolismen
dc.subject.otherFastingen
dc.subject.otherGlucose.pharmacologyen
dc.subject.otherHarmine.analogs & derivatives.metabolismen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherLactates.analysisen
dc.subject.otherLactic Aciden
dc.subject.otherLiver.metabolismen
dc.subject.otherMaleen
dc.subject.otherOxygen Consumptionen
dc.subject.otherPerfusionen
dc.subject.otherPyruvates.analysisen
dc.subject.otherPyruvic Aciden
dc.subject.otherRatsen
dc.subject.otherRats, Inbred Strainsen
dc.subject.otherUridine Diphosphate Glucuronic Acid.metabolismen
dc.titleSynergistic effects of hypoxia and fasting on harmol elimination in the isolated perfused rat liver.en
dc.typeJournal Articleen
dc.identifier.journaltitleBiochemical pharmacologyen
dc.identifier.affiliationUniversity of Melbourne, Department of Medicine, Austin Hospital, Victoria, Australiaen
dc.description.pages1207-12en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/3355595en
dc.type.austinJournal Articleen
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.languageiso639-1en-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
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