title: Short fasting does not protect perfused ex vivo rat liver against ischemia-reperfusion. On the importance of a minimal cell energy charge.
abstract: OBJECTIVE
  Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting.
  
  
  METHODS
  Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers.
  
  
  RESULTS
  Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate.
  
  
  CONCLUSIONS
  High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role.
authors.affiliation: Laboratory of Experimental Medicine (ULB Unit 222), University Hospital Center, Charleroi, Belgium.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Papegay
authors.affiliation: Laboratory of Experimental Medicine (ULB Unit 222), University Hospital Center, Charleroi, Belgium.
authors.forename: Michaela
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Laboratory of Experimental Medicine (ULB Unit 222), University Hospital Center, Charleroi, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Nuyens
authors.affiliation: Laboratory of Molecular Biology of the Gene, Department of Molecular Biology, Free University of Brussels (ULB), Gosselies, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Kruys
authors.affiliation: Laboratory of Experimental Medicine (ULB Unit 222), University Hospital Center, Charleroi, Belgium.
authors.forename: Jean G
authors.initials: JG
authors.lastname: Boogaerts
authors.affiliation: Inserm, CHU Lille, Biochemistry and Molecular Biology, CBP and University Lille, CHRU Lille, EA 7364, RADEME - Maladies Rares du Développement et du Métabolisme: Du Phénotype au Génotype et à la Fonction, France. Electronic address: Joseph.vamecq@inserm.fr.
authors.forename: Joseph
authors.initials: J
authors.lastname: Vamecq
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D031204:Caloric Restriction; D045304:Cytochromes c / Q000378:metabolism; D005215:Fasting; D005260:Female; D006003:Glycogen / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D013997:Time Factors
chemical_list: D006003:Glycogen; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011188:Potassium
keywords: Ex vivo perfused liver; Feeding; In situ perfused liver; Short fasting