Cold preservation mediated renal injury: involvement of mitochondrial oxidative stress.
Cold preservation has greatly facilitated the use of cadaveric kidneys for renal transplantation, but, clearly, damage occurs during both the preservation episode and the reperfusion phase (following transplantation). The aims of this study were twofold: to develop an in vivo model that was capable of evaluating renal function at early time points following cold preservation, and to evaluate the extent of renal mitochondrial damage that occurs following short periods of cold preservation in vivo. To accomplish these goals, we developed a novel rat model of in vivo renal cold ischemia followed by warm reperfusion (cold I/R) which avoided the complexity involved with transplantation. Briefly, after a right nephrectomy, cold I/R was initiated via pulsatile perfusion (40 minutes) of the left kidney with a cold University of Wisconsin solution followed by 18 hours of warm reperfusion. Cold I/R resulted in significant renal injury, nitrotyrosine production, and inactivation of the key mitochondrial antioxidant enzyme, manganese superoxide dismutase. Furthermore, the activities of the mitochondrial respiratory complexes were significantly reduced following cold I/R. In conclusion, short-term cold I/R results in inactivation of MnSOD, which may lead to the inhibition of mitochondrial complexes and subsequent renal injury. These data suggest that compounds designed to prevent early mitochondrial injury in kidneys that undergo cold preservation would significantly improve renal function and graft survival following transplantation.
Saba
Hamida
H
Department of Pharmacology/Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Munusamy
Shankar
S
Macmillan-Crow
Lee Ann
LA
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D015925:Cryopreservation / Q000379:methods*; D004195:Disease Models, Animal; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning / Q000009:adverse effects / Q000379:methods; D007668:Kidney; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008928:Mitochondria / Q000473:pathology*; D009926:Organ Preservation / Q000009:adverse effects* / Q000379:methods; D018384:Oxidative Stress; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013482:Superoxide Dismutase / Q000378:metabolism
D013482:Superoxide Dismutase