Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.
BACKGROUND
In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused rat kidney (IPK) model both after cold perfusion (CP) and after cold storage (CS). We hypothesized that in the CP model iron-dependent cold-induced injury is more pronounced, since oxygen is constantly provided.


METHODS
The IPK was either flushed with University of Wisconsin (UW) solution and stored for 4, 18 or 24 h at 4 degrees C or perfused during 4 h at 4 degrees C with UW for machine perfusion. The iron chelators 2,2'-dipyridyl or desferal, or the negative control 4,4'-dipyridyl were added during the cold perfusion. Kidney function was measured during 2 h reperfusion at 37.5 degrees C and compared to a control group (without cold preservation).


RESULTS
Compared to control perfusion, kidney function was decreased in all experimental protocols. glomerular filtration rate and FR(H2O) were significantly decreased, while FE(gluc) and FE(Na) were higher after 4 h CS and CP. After 4 h CP, also renal vascular resistance was increased. Addition of 2,2'-dipyridyl did not improve kidney function after either CS or CP. Prolonged periods of CS worsened kidney function. The addition of 2,2'-dipyridyl or desferal did not improve kidney function after longer periods of CS.


CONCLUSIONS
Addition of an iron chelator to the preservation solution UW did not improve kidney function after both CS and CP. Iron chelation is not able to prevent cold-induced damage in the isolated perfused rat kidney.
Bartels-Stringer
Miranda
M
Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Wetzels
Jack F M
JF
Wouterse
Alfons C
AC
Steenbergen
Eric
E
Russel
Frans G M
FG
Kramers
Cornelis
C
D000818:Animals; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007036:Hypothermia, Induced / Q000009:adverse effects*; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors
D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species