Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats

Abstract

PURPOSE:To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline. METHODS:It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/ kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3. RESULTS:The values of sO 2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR). CONCLUSION:The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.

The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats

“…In the IR-PTX group, we found that the villi were well preserved, the leukocytes were less conspicuous, and the capillaries were dilated. Corroborating our findings, previous reports described more severe villous lesions in animals subjected to IR without any treatment compared to animals subjected to PTX treatment 13,17,18,[22][23][24][25] . Other reports using PTX at concentrations less than or equal to the concentrations used in this study have reported the preservation of the villi in the intestinal epithelium, similar to the results described here 13,17,18,[22][23][24][25][26] .…”

“…The discovery that PTX had an anti-TNF-α effect stimulated its application into organ ischemia 13,14,19,[21][22][23] . PTX is a nonselective phosphodiesterase inhibitor 12,14,18,19 that decreases TNF-alpha and NFkB gene transcription 13,14,19 , affecting multiple steps in the cytokine/chemokine pathways and exerting beneficial immunomodulatory effects on inflammatory conditions directly and indirectly 12,13,[21][22][23][24][25][26][27] . PTX increased the levels of specific cytokines, increased cyclic adenosine monophosphate (cAMP) levels and decreased TNF-alpha levels, resulting in anti-inflammatory and antioxidant properties 12,18,21,23,25,26 .…”

Pentoxifylline exerts anti-inflammatory effects on cerebral ischemia reperfusion‑induced injury in a rat model via the p38 mitogen-activated protein kinase signaling pathway

“…The results of the current study demonstrated that pretreatment with pentoxifylline significantly suppressed IL-6 and TNF-α levels, inhibited MDA and increased SOD levels, and reduced COX-2 mRNA and protein expression in cerebral IRI rats. Marques et al (24) reported that pentoxifylline may attenuate the inflammatory process and apoptosis via cleaved caspase-3 and COX-2 in rats with intestinal IRI. In addition, Mayyas et al (25) observed that pentoxifylline suppressed myocardial oxidative status following intake of a western diet.…”

Teobromin STI571’in Apoptotik Etkinligini Artirir mi?

“…STI571, hücre tipine göre TNF bağımlı ya da bağımsız olacak şekilde farklı tipte kaspazları aktive ederek apoptozisi uyarır (11,12). Daha önce yapılan çalışmalarla kakao metabolitleri olan kateşinler, pentoksifilin, prosiyanidin ve fenoliklerin bazı hayvan modelleri ve kanser hücrelerinde farklı kaspaz seviyelerini artırdığı (13,14) ve bunu da TNFα ve buna bağlı hücre içi sinyal yolaklarının (MAPK) yanı sıra siklinler, p21 ve p27 üzerinden yaptığı belirlenmiştir (10). Teobromin MAPK, Akt/mTOR ve NFκB yolağını baskılayıp p38 ve JNK aktivitesini artırarak hücre büyümesini engeller.…”