Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution.
Very little is known about iron metabolism and the mediators of iron metabolism in liver subjected to cold storage before transplantation. Therefore, in this study, we investigated the effect of cold storage on iron homeostasis in the rat liver. When livers were stored at 4 degrees C in University of Wisconsin solution for up to 6 and 24 hours, significant increases occurred in the labile iron pool, ferritin protein, and heme oxygenase activity. Significant decreases in heme content and iron regulatory protein 1 and 2 binding activities occurred by 24 hours. Liver injury indicated by significant increases in University of Wisconsin solution transaminase activity and liver lipid hydroperoxide levels occurred by 6 and 24 hours. Taken together, these results suggest that during pretransplantation cold storage of the liver, an aberrant iron homeostasis develops that contributes to preservation injury, and predisposes the liver to reperfusion injury by iron-dependent reactive oxygen species/Fenton reaction.
Wyllie
Samuel
S
Michael E. Debakey Department of Surgery, The Methodist Hospital/Baylor College of Medicine Liver Center, Baylor College of Medicine, Houston, TX 77030, USA.
Seu
Philip
P
Gao
Feng Q
FQ
Goss
John A
JA
D000241:Adenosine / Q000737:chemistry; D000493:Allopurinol / Q000737:chemistry; D000597:Amino Acids, Branched-Chain / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D015925:Cryopreservation; D005293:Ferritins / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000737:chemistry; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008297:Male; D009926:Organ Preservation / Q000009:adverse effects*; D019188:Organ Preservation Solutions / Q000737:chemistry; D018384:Oxidative Stress; D011887:Raffinose / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D008054:Lipid Peroxides; D019188:Organ Preservation Solutions; D011990:Receptors, Transferrin; C055206:University of Wisconsin-lactobionate solution; D006418:Heme; D000493:Allopurinol; D005293:Ferritins; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D001219:Aspartate Aminotransferases; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose