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 fasting. Methods Perfused ex vivo livers using shortly (18 hours) fasted compared to fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores differently available in time and cell energetic charges (ratio of ATP plus half of the ADP concentrations to the sum of ATP+ADP+AMP concentrations), adenosine phosphates and glycogen were further measured at different time points in livers. Results Short fasting vs 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 vs feeding was associated with lower glycogen and energetic charges in livers, and lower lactate levels in the perfusate. Conclusion High energetic charge, intracellular content in glycogen and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question for much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it puts forwards that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role.