Mannitol attenuates kidney damage induced by xanthine oxidase-associated pancreas ischemia-reperfusion.
BACKGROUND
Ischemia and subsequent reperfusion (IR) may induce local and remote organ reperfusion injury. It may be propagated by xanthine oxidase (XO)-generated oxidant stress. We investigated whether pancreas IR directly and acutely induces renal dysfunction and if this outcome could be prevented by mannitol.


METHODS
Rat pancreases were isolated and perfused with Krebs-Henseleit solution enriched with 5% bovine albumin. Other rats donated kidneys that were perfused at constant pressure mode. Each pancreas underwent 45 min of either perfusion (control) or ischemia (no flow). Both organ perfusion systems were then combined and the kidneys were perfused with the pancreatic 15-min reperfusate for 2 h. A third group consisted of paired ischemic pancreases and nonischemic kidneys treated with mannitol 250 mg/kg body weight during reperfusion.


RESULTS
The controls demonstrated no abnormal perfusion or metabolite changes. Pancreas and renal perfusion pressures increased by >50% in the ischemia group immediately upon reperfusion; it remained above the values of controls during the 2-h kidney reperfusion. Conversely, perfusion pressure in the treatment group was not significantly different from the control. The reduced glutathione level increased significantly, as did XO, immediately upon starting reperfusion in both organs appertaining to the ischemic group; this misbalance was not documented in the controls and the mannitol-treated groups. Urine output was severely reduced in the IR kidneys.


CONCLUSIONS
Ischemia/reperfusion of the rat pancreas evokes immediate renal dysfunction. Kidney oxidant-antioxidant balance is disturbed, but can be prevented with mannitol. These two figures underline the role of oxidative stress in promoting acute renal damage in the presence of pancreas IR.
Khoury
Wisam
W
Division of Surgery B, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Namnesnikov
Michael
M
Fedorov
Dimitri
D
Abu-Gazala
Samir
S
Abu-Ghazala
Samir
S
Weinbroum
Avi A
AA
D000818:Animals; D004234:Diuretics, Osmotic / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D018384:Oxidative Stress; D010179:Pancreas / Q000098:blood supply* / Q000201:enzymology; D016035:Pancreas Transplantation; D010195:Pancreatitis / Q000150:complications; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D014969:Xanthine Oxidase / Q000378:metabolism*
D004234:Diuretics, Osmotic; D008353:Mannitol; D014969:Xanthine Oxidase