Pentoxifylline in Ischemia-Induced Acute Kidney Injury in Rats

Abstract

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 hmol O 2 /mg protein/min compared to 8.9 ± 1.4 hmol 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 ± 2.1hmol 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.

Nephroprotective Effect of Pentoxifylline in Renal Ischemia–Reperfusion in Rat Depends on the Timing of Its Administration

“…In this context, mycophenolate mofetil has recently been reported to reduce expression of the monocyte Toll-like receptor 4 and improve the course of IRI and iAKI in mice when given for 2 days before renal ischemia [20]. Of note, in compliance with our results, Okumura et al [21] showed no nephroprotective effect of PTX in the model of iAKI in rat when the drug was administered during reperfusion of the ischemic kidney.…”

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

“…32 PTX has been shown to improve tissue oxygenation and endothelial function and to inhibit proinflammatory cytokine production. 8 In the present study, PTX improved tissue oxygenation by a reduction in oxidative stress but this was not sufficient for preservation of renal function. Although downregulation of proinflammatory cytokines seems to be important for the protection or attenuation of injury it is possible that mitochondria were already highly damaged by the ischemic process.…”

“…8 PTX also inhibits cell proliferation and extracellular matrix accumulation. Human studies have proved its antiproteinuric effect in patients with glomerular diseases.…”

Effect of pentoxifylline on preventing acute kidney injury after cardiac surgery by measuring urinary neutrophil gelatinase - associated lipocalin

“…It can also affect the microcirculatory blood flow and contribute to the attenuation of interstitial inflammation, down regulation of monocyte chemo-attractant protein-1 gene expression, reduction in the expression of mitogenic and profibrogenic genes, and suppression of the proliferation of interstitial fibroblast and glomerulomesangial cells [8]. However, the preclinical data with regard to PTX and AKI seems controversial [9,10]. The effect of PTX in reducing renal injury by measuring sCr and α-1-microglobulin was investigated and ameasuring sCr and beneficial role of PTX on the prevention of kidney injury was observed [11].…”