Enhanced energy metabolism during cold hypoxic organ preservation: studies on rat liver after pyruvate supplementation.
Previous studies have indicated that pyruvate is able to reduce ischaemia/reperfusion (I/R) injury in a variety of tissues, but a full understanding of the effects is lacking. In this current preliminary study, magnetic resonance spectroscopy (MRS) was used to investigate the biochemical effects of differing concentrations of pyruvate (3 and 15mM) on liver metabolism during the cold hypoxic preservation period itself, in order to gain insight into possible mechanisms. Hepatic lactate, alanine, and succinate levels were increased in livers preserved with 15mM pyruvate added to the University of Wisconsin (UW) solution and were generally elevated (but to a lesser degree) in livers flushed with 3mM pyruvate, compared to those cold stored in UW alone. Further, from enzymatic assays of adenine nucleotides, 15mM levels of pyruvate were found to maintain higher ATP levels during short periods (up to 4h) of cold hypoxic storage than in UW stored livers, whilst energy charge ratios (after 4 and 24h) were also higher (P<0.01 in each case). This may arise from enhanced glycolysis secondary to an improved redox status in the pyruvate-treated livers, as evident by the increase in the levels of lactate.
So
Po-Wah
PW
Imperial College School of Medicine, Biological Imaging Centre, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK.
Fuller
Barry J
BJ
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015925:Cryopreservation; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004734:Energy Metabolism / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D019188:Organ Preservation Solutions; D009994:Osmolar Concentration; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000378:metabolism
D004338:Drug Combinations; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D019344:Lactic Acid; D000493:Allopurinol; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D000409:Alanine