Chu SRS 2011
|Chu MJJ, Hickey AJ, Tagoloa S, Zhang L, Dare A, MacDonald J, Yeong M, Bartlett A, Phillips A (2011) Hepatic mitochondrial dysfunction during cold ischaemia. SRS Adelaide 2011.|
Aim: To determine the impact of cold ischaemia on hepatic mitochondrial function in University of Wisconsin (UW) solution in the setting of hepatic steatosis.
Methods: Livers were harvested from 10-week old genetically obese (ob/ob, n = 9) or lean C57 control mice (n = 9); and preserved in ice-cold UW solution. Mitochondrial function analysis was performed on permeabilised liver samples using a substrate and inhibitor titration protocol in conjunction with a high-resolution respirometer (OROBOROS® Oxygraph-2k) at multiple time-points over 24 h during cold ischemia (CI).
Results: Ob/ob mice livers and control mice livers showed either severe (> 60%) or no macrovesicular steatosis respectively. Mitochondria from ob/ob mice livers demonstrated a faster and greater decrease in the percentage of respiration contributing to oxidative phosphorylation over 24 hours of cold storage compared to control mice. After 12 hours of CI, there was also an increased dependence on Complex II respiration relative to Complex I in ob/ob mice livers suggestive of Complex I damage and potential loss of key ATP synthesis efficiency.
Conclusion: There was a time-dependant damage of hepatic mitochondrial function during CI. Steatotic livers demonstrated greater mitochondrial dysfunction during CI compared to lean livers.
• Keywords: hepatic mitochondrial dysfunction, cold ishaemia
• O2k-Network Lab: NZ Auckland Hickey AJ
Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Liver Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase