Pentoxifylline Protects the Small Intestine After Severe Ischemia and Reperfusion
| Autor: | Alexander H. Toledo, José Miguel Lloris Carsi, Dolores Cejalvo Lapeña, Cristobal Zaragoza Fernandez, Luis Horacio Toledo Pereyra |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Time Factors medicine.medical_treatment Interleukin-1beta Ischemia Protective Agents Gastroenterology Pentoxifylline chemistry.chemical_compound Malondialdehyde Internal medicine medicine.artery Intestine Small Mesenteric Vascular Occlusion Laser-Doppler Flowmetry medicine Animals Splanchnic Circulation Superior mesenteric artery Rats Wistar Saline Peroxidase Transplantation L-Lactate Dehydrogenase Interleukin-6 Tumor Necrosis Factor-alpha Vascular disease business.industry medicine.disease Small intestine Rats Surgery Disease Models Animal medicine.anatomical_structure Neutrophil Infiltration chemistry Cytoprotection Reperfusion Injury Inflammation Mediators business Reperfusion injury Biomarkers Blood Flow Velocity medicine.drug |
| Zdroj: | Experimental and Clinical Transplantation. 11:250-258 |
| ISSN: | 2146-8427 1304-0855 |
| Popis: | 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-A±, interleukin-1A², 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 damage - specifically, serum lactic acid dehydrogenase, and tissue malondialdehyde, ischemia, and reperfusion. Additionally, we saw decreased levels of tumor necrosis factor-A±, interleukin-1A², 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. |
| Databáze: | OpenAIRE |
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