Pentoxifylline in ischemia-induced acute kidney injury in rats.
Ischemia is an important cause of acute kidney injury (AKI). Pentoxifylline has been shown to improve tissue oxygenation and endothelial function and inhibit proinflammatory cytokine production. The aim of this study was to evaluate a possible renal protective effect of pentoxifylline against ischemia by measuring mitochondrial respiratory metabolism as an index of cell damage. Rats were submitted to right nephrectomy. The left kidney was submitted to ischemia by clamping the renal artery for 45 minutes. Immediately after release of the clamp, 1 mL of a solution containing 20 mg of pentoxifylline/mL was injected intravenously, while a control group received 1 mL of normal saline intravenously. Five minutes after the injection, the left kidney was removed, homogenized, and subjected to refrigerated differential centrifugation. Mitochondrial respiratory metabolism was measured polarographically. The mitochondria isolated from the kidneys of saline-treated rats had an endogenous respiration of 9.20 +/- 1.0 etamol O(2)/mg protein/min compared to 8.9 +/- 1.4 etamol O(2)/mg protein/min in the pentoxifylline-treated rats (p > 0.05). When stimulated by sodium succinate, the respiratory metabolism increased in a similar fashion in both groups of animals: 17.9 +/- 2.3 and 18.1 +/- 2.1 etamol O(2)/mg protein/min in the untreated and pentoxifylline-treated groups, respectively (p > 0.05). In the present study, pentoxifylline was not found to exert any protective effect on the kidney. It is possible that at the time of pentoxifylline administration, the mitochondria had already been damaged by the process of ischemia, and its effect may have been insufficient to reverse cell damage.
Okumura
Alice S
AS
Renal Service, Federal University of Bahia, School of Medicine, Salvador, Bahia, Brazil.
Rodrigues
Luiz Erlon
LE
Martinelli
Reinaldo
R
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D010431:Pentoxifylline