Effects of thalidomide and pentoxyphylline over local and remote organ injury after intestinal ischemia/reperfusion

Transplant Proc. 2010 Jun;42(5):1624-6. 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)-alpha 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-alpha 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-alpha, 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-alpha levels.

Conclusion: Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-alpha and lipid peroxidation. However, combination treatment showed small, additive effects.

MeSH terms

  • Animals
  • Aspartate Aminotransferases / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Intestinal Mucosa / metabolism
  • Intestines / blood supply*
  • 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
  • Pentoxifylline / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / blood*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Thalidomide / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Pentoxifylline