Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress

Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):194-200. doi: 10.1016/s1499-3872(15)60348-4.

Abstract

Background: Liver ischemia reperfusion (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury. This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury.

Methods: Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase.

Results: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion.

Conclusion: This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Capillary Permeability / drug effects*
  • Disease Models, Animal
  • Drug Synergism
  • Evans Blue / pharmacology*
  • Free Radical Scavengers / therapeutic use*
  • Interleukin-1 / blood
  • Interleukin-10 / blood
  • Ischemia / complications
  • Lipid Peroxidation / drug effects
  • Liver Diseases / etiology
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Lung / blood supply
  • Lung / enzymology
  • Male
  • Oxidative Stress / drug effects*
  • Pentoxifylline / therapeutic use*
  • Permeability / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Saline Solution, Hypertonic / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Free Radical Scavengers
  • Interleukin-1
  • Saline Solution, Hypertonic
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Evans Blue
  • Peroxidase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Pentoxifylline