Effects of Thalidomide and Pentoxyphylline Over Local and Remote Organ Injury After Intestinal Ischemia/Reperfusion

• Published in: Transplantation proceedings 2010-06, Vol.42 (5), p.1624-1626
• Main Authors: Cámara-Lemarroy, C.R, Guzmán-de la Garza, F.J, Alarcón-Galván, G, Cordero-Pérez, P, Muñoz-Espinosa, L.E, Fernández-Garza, N.E
• Format: Article
• Language: English
• Subjects: Animals; Aspartate Aminotransferases - blood; Biological and medical sciences; Enzyme-Linked Immunosorbent Assay - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; Intestines - blood supply; Intestines - metabolism; Intestines - pathology; L-Lactate Dehydrogenase - blood; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - physiology; Liver - physiopathology; Lung - drug effects; Lung - physiology; Lung - physiopathology; Male; Medical sciences; Other diseases. Semiology; Pentoxifylline - therapeutic use; Rats; Rats, Wistar; Reperfusion Injury - blood; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Thalidomide - therapeutic use; Tissue, organ and graft immunology; Tumor Necrosis Factor-alpha - blood
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.12.074

Abstract Objective We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat. Materials and Methods Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema. Results Serum concentrations of AST, LDH, and TNF-α were increased after I/R in the CTL compared with the SHAM group ( P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased ( P < .05). The W/D ratio was elevated in all tissue samples as well ( P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-α, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R ( P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-α levels. Conclusion Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-α and lipid peroxidation. However, combination treatment showed small, additive effects.