Pentoxifylline attenuates ischemia/reperfusion injury to the small intestine in the rat

Udassin, Raphael; Vromen, Amos; Seror, Dan; Haskel, Yuval

doi:10.1007/bf00497805

Cited by 7 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[44][45][46] This is the first study of a small intestinal ischemia used for survival of more than a few hours when evaluating the clinical response of ischemic injured small bowels. [27][28][29][30][31][32] In fact, survival in this study was extended to 7 days to demonstrate the complete effect of PTX pharmacological treatment on this important clinical endpoint. Only 1 other work by Tireli and associates 4 used 7-day testing, but in a different context, where PTX was used to observe its effect on healing of ischemic small intestine anastomoses.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28][29][30][31][32] A search of the literature using the wording "pentoxifylline in intestinal ischemia" returned only 25 articles between1992 and the date of this study, of which, only 5 studies were similar to our current work. [28][29][30][31][32] However, when we searched more general wording "pentoxifylline in ischemia," we found 307 articles. This led us to believe that the interest in using PTX has not been in small intestinal ischemia but rather, on other types of ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

“…Others followed. [29][30][31][32] The discovery that PTX had an anti-TNF-α effect a few years earlier, stimulated its application into organ ischemia. 33 This study sought to define the role of PTX in severe intestinal ischemia when all clinical (survival), laboratory (molecular), and pathological parameters were evaluated together in a well-accepted model of small intestinal ischemia.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Carsí

Cejalvo‐Lapeña

Toledo³

et al. 2013

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: Pentoxifylline, a methylxanthine derivative with significant hemorheologic properties, is used for claudication in patients with peripheral vascular disease, and experimentally for ischemic injury to organs because of its antioxidant and antiinflammatory effects. We used a rat model of severe small intestinal ischemia and reperfusion to determine the ability of pentoxifylline in improving survival, molecular response, and pathological protection. Materials and Methods: We used 6 groups of male Wistar rats (n=25 each). The superior mesenteric artery was occluded for 120 minutes. Laboratory and tissue studies were done on 5 animals, 1 hour after reperfusion, and animal survival was assessed at 7 days. There were 2 control groups that received normal saline, either before ischemia or during reperfusion. The 4 treated groups received pentoxifylline 1 or 10 mg/kg at the same times mentioned above. Laboratory studies included measuring serum lactic acid dehydrogenase, tumor necrosis factor-α, interleukin-1β, and interleukin-6. Intestinal tissue malondialdehyde and myeloperoxidase in small intestine tissue also were measured. Histology and laser vascular blood flow at baseline and reperfusion were obtained, and survival was determined 7 days after ischemia.Results: A significant survival benefit in the animals treated with 10 mg/kg of pentoxifylline at reperfusion was noted. This coincided with a reduction in biochemical markers of cell damagespecifically, serum lactic acid dehydrogenase, and tissue malondialdehyde, ischemia, and reperfusion. Additionally, we saw decreased levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Improved postreperfusion blood flow shown by laser Doppler technology also was seen in the treated groups. Histologically, we observed less neutrophil infiltration in the intestine of ischemic-treated rats. Also seen in the control animals were increased necrotic lesions in the microvilli with a higher presence of lysozyme in the Paneth cells. Survival was significantly better at 7 days (70% vs 40%) when we compared the pentoxifylline group treated at reperfusion (10 mg/kg) to the ischemic controls. Conclusions: Pentoxifylline had a significant protective effect on severely ischemic bowel when administered during reperfusion at a dosage of 10 mg/kg. Better survival, improved histology, and molecular response should urge consideration of the consideration of applying these findings in some general surgery and transplant conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Carsí

Cejalvo‐Lapeña

Toledo³

et al. 2013

Exp Clin Transplant

View full text Add to dashboard Cite

show abstract

“… 7 , 15 , 18 – 22 Few studies reported in the literature have addressed the role of PTX in small intestinal I/R. 7 , 15 , 18 – 23 The present study on the mechanisms underlying the protective effect of PTF in small intestinal ischemia specifically suggests that the anti-inflammatory action of PTF is very important. This study indicates that PTX reduces the levels of TNFα, IL-1β, and IL-6 after severe organ ischemia in rats, which may have important implications for ischemia outcomes because these three proinflammatory cytokines are regulators of the inflammatory response in human and animal ischemic cells.…”

Section: Discussionmentioning

confidence: 75%

“…Our findings are similar to those of other studies that investigated the effects of PTF on ischemic small bowel injury. 7 , 15 , 18 – 22 …”

Section: Discussionmentioning

confidence: 99%

Protective effects of pentoxifylline in small intestine after ischemia–reperfusion

et al. 2018

View full text Add to dashboard Cite

ObjectiveThis study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine.MethodsThirty-six Wistar albino rats were divided into six groups. The superior mesenteric artery was clamped for 120 minutes, and reperfusion was performed for 60 minutes. Saline (0.4 mL), pentoxifylline (1 mg/kg), and pentoxifylline (10 mg/kg) were intraperitoneally administered to the rats in the C1, P1, and P3 groups, respectively, 60 minutes before ischemia and to the rats in the C2, P2, and P4 groups, respectively, during reperfusion onset. Malondialdehyde, myeloperoxidase, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 in serum and tissue were measured by enzyme-linked immunosorbent assay. Intestinal ischemic injury was histopathologically evaluated by the Chiu score and immunohistochemical staining.ResultsAll serum and tissue molecular responses were significantly blunted in the pentoxifylline-treated groups compared with the controls. Significant improvement in ischemic damage was demonstrated in the pentoxifylline-treated groups by histological grading and immunohistochemical scoring.ConclusionsThe protective effects of pentoxifylline were confirmed by molecular responses and histopathological examination.

show abstract

Amelioration of Ischemia‐Reperfusion Injury in Rat Intestine by Pentoxifylline‐Mediated Inhibition of Xanthine Oxidase

Hammerman,

Goldschmidt,

Caplan

et al. 1999

J. pediatr. gastroenterol. nutr.

View full text Add to dashboard Cite

Background:Intestinal ischemia‐reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR.Methods:Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid‐reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase‐xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology.Results:Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidase‐xanthine dehydrogenase ratios were elevated only in IR/Placebo (0.67 ± 0.22 vs. 0.45 ± 0.14 in IR/PTX; 0.42 ± 0.22 in No IR/Placebo; and 0.40 ± 0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 ± 1.35 vs. 46.1 ± 7.0 in IR/Placebo; 41.1 ± 2.5 in No IR/Placebo; 43.6 ± 1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups.Conclusions:Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase‐xanthine dehydrogenase ratios in the treated compared with IR‐only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.

show abstract

Pentoxifylline attenuates ischemia/reperfusion injury to the small intestine in the rat

Cited by 7 publications

References 39 publications

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Protective effects of pentoxifylline in small intestine after ischemia–reperfusion

Amelioration of Ischemia‐Reperfusion Injury in Rat Intestine by Pentoxifylline‐Mediated Inhibition of Xanthine Oxidase

Contact Info

Product

Resources

About