The effects of pentoxifylline into the kidneys of rats in a model of unilateral hindlimb ischemia/reperfusion injury

Abstract

PURPOSE: To study the role of pentoxifylline (PTX) on remote kidney injury caused by muscle ischemia of left hindlimb of rats. METHODS: After xylazine and ketamine anesthesia, the left hindlimb of rats (n=66) were submitted to 6 hours ischemia (clamping the left common iliac artery). Three groups were used: sham group (SG, n=6), early group (EG, n=30) with reperfusion after 4 hours and late group (LG, n=30) with reperfusion after 24 hours. The saline solution (EG1, n=10 and LG1, n=10) or PTX (40mg.Kg-1) was administered in the reperfusion beginning (EG2, n=10/LG2, n=10) or divided in two doses in the ischemia beginning and reperfusion beginning (EG3, n=10/LG3, n=10). The plasmatic creatinokinase, urea, creatinine, sodium and potassium values were measure and histological samples from left kidney were prepared and H&E stained for scored cellular necrosis and degeneration of kidney tubules and thickness glomerulus determination. The apoptosis index was determined by immunohistochemical expression of the caspase-3. The tests of Mann-Whitney and Kruskal-Wallis (p < 0.05) were applied. RESULTS: The urea (90.5 ± 30.96 mg.dL-1), creatinine (2.28 ± 0.54 mg.dL-1), potassium (16 ± 3.66 mmol.dL-1) and mesangium thickness (0.97 ± 0.42 µm) values were significantly higher in group LG3. There was no significantly difference of caspase 3 expression between EG2 (16.35 ± 1.65%) and LG3 (15.57 ± 2.54%), and both were significantly worse than SG (9.8 ± 1.98%). CONCLUSIONS: The PTX has some protecting effect on remote kidney injury due to hindlimb ischemia/reperfusion injury only in the early phase of reperfusion.

Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model

“…In addition, the high metabolic demands of active tubular re-absorption make the kidney particularly vulnerable to ischemic injury. 25,26 Curcumin, a phytochemical derived from the rhizome of the curcuma longa plant, has been shown to have anticancer, antimicrobial, 27 hepatoprotective, 28 and antihyperlipidemic properties. 29 Recent studies proved the ability of curcumin and related compounds to inhibit free radical generation in vitro and in vivo in different organs, such as the lungs, brain, and heart [30][31][32] and curcumin is also shown to inhibit neutrophil infiltration.…”

Ischemia and reperfusion of rat small intestine using pentoxyfilline and prostaglandin E1

“…At those areas the integrity of cell membrane could suffer with hypoxia and the cell itself could miss the ideal amount of energy production as well as accumulate, direct or indirectly, metabolites and inflammatory mediators causing cellular dysfunction [9][10][11][12][13][14][15] .…”

Effects of pentoxifylline on proliferation of human umbilical vein endothelial cells (HUVEC)

“…Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholinemediated vasorelaxation 5 . There are several studies examined the preventive effect of PTX on endothelial damage in laboratory conditions as ischemia reperfusion studies [5][6][7][8] . Although beneficial effects of PTX have demonstrated on disorders related to the microcirculation of tissues, the mechanisms by which PTX exerts a protective effect are not fully understood 9 .…”

“…Therefore, several studies demonstrated its hemorheological properties as well as an inhibitor of inflammatory cytokines 9 . In recent years, there is an increased interest to PTX as a study drug in ischemia and reperfusion studies 8,9,12 . Genovés et al 9 reviewed the status of PTX on ischemia and reperfusion studies in liver and they noted that PTX has a potential to be used as a preventive drug and its effect seems to related to mainly TNFalpha.…”