Role of Diltiazem in Ischemia-Reperfusion Injury of the Intestine

Mustafa, Nilofar; Yandi, Mustafa; Turgutalp, Havvanur; Ovalı, Ercüment; Aydemir, Vedat; Albayrak, Levent

doi:10.1159/000129354

Cited by 20 publications

(26 citation statements)

References 16 publications

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“…[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%

“…23 In this regard, in the late 1980s Waxman 24 and Coccia, 25 and a few years later, Flynn 26 and Sakio 27 and associates, among others, recognized the positive blood flow effects of PTX in hemorrhagic conditions. Mustafa in 1995 28 used PTX in a typical rat small bowel ischemic model as an anti-ischemic drug. Others followed.…”

Section: Introductionmentioning

confidence: 99%

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Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Carsí

Cejalvo‐Lapeña

Toledo³

et al. 2013

Exp Clin Transplant

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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

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“…Improved anastomotic healing following pentoxifylline treatment has been demonstrated in ischemia-reperfusion models (23). Pentoxifylline has also been shown to improve hemodynamic function and reduce plasma TNF-␣ levels and mortality in preterm neonates with blood culture-positive sepsis (24,25).…”

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confidence: 99%

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

et al. 2006

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Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor alpha (TNF-␣) has been shown to play a central role in the inflammatory cascade leading to the development of NEC. Published evidence points to a significant role of pentoxifylline in inhibition of TNF-␣ and in reducing mucosal injury and improving healing in ischemiareperfusion experiments. Our aim was to investigate the effect of pentoxifylline on the incidence of NEC in a neonatal rat model. Newborn Sprague-Dawley rat pups originating from eight separate litters were delivered by cesarean section at 21.5 d and were formula fed from birth by orogastric gavage. The rat pups were randomized to receive either intraperitoneal pentoxifylline (15 mg/kg/dose) or placebo, given every 8 h beginning at 24 h of age, in a blinded fashion. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4°C for 10 min. The animals were euthanized at development of NEC or at 96 h and intestinal tissue was processed and examined for histologic changes of NEC. The incidence of NEC was significantly lower in the pentoxifylline group [pentoxifylline 5/38 versus placebo 15/36; p ϭ 0.008, odds ratio (OR) ϭ 0.21 95% confidence interval (CI) 0.07-0.67]. Among the pups developing NEC, significantly fewer rat pups treated with pentoxifylline had severe (Ն3) intestinal injury scores [pentoxifylline 1/5 versus placebo 10/15; p ϭ 0.031, OR 0.06, 95% CI 0.01-0.79]. We conclude that intraperitoneal administration of pentoxifylline significantly reduced the incidence and severity of NEC in our experimental animal model. (Pediatr Res 60: 185-189, 2006)

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“…Other agents were used seeking to attenuate the injuries caused by ischemia-reperfusion without, however, using NEC as an experimental model. Such was the case of: glucagon 13 , 21-amino-steroids 14 , pentoxifylline 15 , somatostatin 16 and perfluorocarbons 17 . More recently, by using a model of HR in rats, glycine was put to the test as a protective agent of intestinal injuries stemming there from [18][19][20] .…”

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confidence: 99%

Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats

et al. 2006

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Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats 8 -ORIGINAL ARTICLE Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats 1Glicina reduz a peroxidação lipídica tecidual em enterocolite necrosante induzida por hipóxia-reoxigenação em ratos ABSTRACT Purpose:To assess the protective effect of glycine in an experimental model of Neonatal Necrotizing Enterocolitis (NEC). Methods: Fifty (50) neonatal Wistar rats, from a litter of six female rats and weighing 4 to 6 grams, were used. Five animals were cannibalized and the 45 remaining were distributed into three groups: the G1 normal control group (n=12); the G2 Group (n=16), of animals that underwent hypoxia-reoxygenation (HR); the G3 Group of animals (n=17) that underwent HR following a 5% intraperitoneal glycine infusion. The animals underwent hypoxia in a CO 2 chamber receiving an air flow of 100% CO 2 for 5 minutes and reoxygenation receiving an O 2 flow at 100% for 5 minutes. One centimeter long small bowel and colon segments were prepared for histological analysis. The rest of the bowel was removed in a block and frozen at minus 80°C for homogenization and determination of tissue malondialdehyde (MDA). Tissue lesions were classified as Grade 0 to Grade 5, according to the level of damaged mucosa. Results: The animals in Group G1 had levels of small bowel and colon lesion significantly smaller as compared to the animals in Groups G2 and G3. The G2 group had mean MDA values significantly higher than the animals in the G1 (p = .015) and G3 (p=0.021) groups. MDA values did not differ significantly (p = 0.992) for the animals in groups G1 and G3. Conclusion: Glycine reduces tissue MDA levels (a measurement of lipid peroxidation) following HR in neonatal rats. Key words: Enterocolitis, Necrotizing. Glycine. Prevention & Control. RESUMO Objetivo:Avaliar o efeito protetor da glicina, num modelo experimental de ECN. Métodos: Foram utilizados 50 ratos Wistar recém-nascidos, com peso variando de 4 a 6 gramas, provenientes da ninhada de seis ratas. Cinco animais foram canibalizados e, os 45 restantes, foram distribuídos em três grupos: controle G1(n=12); G2(n=16), animais que foram submetidos à hipóxia-reoxigenação; G3(n=17), animais submetidos à hipóxia-reoxigenação após uma infusão intraperitoneal de glicina 5%. Os animais foram submetidos à hipóxia em uma câmara de CO 2 recebendo um fluxo de ar contendo 100% de CO 2, durante 5 minutos e à reoxigenação recebendo um fluxo de O 2 a 100% por 5 minutos. Segmentos de intestino delgado e cólon de 1 cm de extensão foram preparados para análise histológica. O restante do intestino foi removido em bloco e congelado a menos 80°C para homogeneização e dosagem de malondialdeído tecidual (MDA). Classificou-se as lesões teciduais de Grau 0 a Grau 5, de acordo com a extensão da lesão mucosa. Resultados: Os animais do Grupo G1 apresentaram graus de lesão de intestino delgado e cólon significantemente menores do que os anima...

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Role of Diltiazem in Ischemia-Reperfusion Injury of the Intestine

Cited by 20 publications

References 16 publications

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats

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