Inflammatory activity modulation by hypertonic saline and pentoxifylline in a rat model of strangulated closed loop small bowel obstruction

Int J Surg. 2014;12(6):594-600. doi: 10.1016/j.ijsu.2014.04.007. Epub 2014 May 4.

Abstract

Background: Intestinal obstruction is an abdominal disease associated to mortality, especially if complicated with sepsis. Resuscitation increases survival, although controversies remain concerning to therapeutic strategy.

Methods: To assess the effects of hypertonic saline and pentoxifylline on the inflammatory response and oxidative stress, Wistar rats underwent a laparotomy loop intestinal obstruction and ischemia. After 24 h, the intestinal segment was resected (IO) without any other treatment and resuscitation/pentoxifylline were administered according to the group: Ringer's lactate (RL); hypertonic saline (HS); pentoxifylline (PTX); Ringer's lactate with pentoxifylline (RL + PTX); hypertonic saline with pentoxifylline (HS + PTX) and the control group (CG) that was not submitted to ischemia and obstruction. Mean arterial pressure (MAP) was recorded 4 times, and euthanasia was done 3 h after the resuscitation to obtain lung tissue, for malondialdehyde (MDA) by thiobarbituric acid reactive substances (TBARS) method, inflammatory cytokines were assessed using ELISA and NF-κΒ by Western blotting.

Results: The initial MAP levels were higher in the RL and HS groups than in the others; however, the last measurement was similar among all the groups. IL-1β, IL-6 and CINC-1 (Cytokine-Induced Neutrophil Chemoattractant-1) were lower in the HS, PTX and HS + PTX groups compared with the IO and RL groups. IL-10 was lower in the HS + PTX group than in the IO group. NF-κB in the HS, PTX and HS + PTX groups were lower than in the IO group; NF-κB in the HS + PTX group was lower than in the RL group. MDA in the lung was lower in the HS + PTX group compared with other groups.

Conclusion: Hypertonic saline and pentoxifylline, both alone and in combination, attenuated oxidative stress and the activation of NF-κB, leading to a decrease in the inflammatory response.

Keywords: Cytokines; Hypertonic saline; Infection; Intestinal obstruction; Oxidative stress; Rehydration solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Drug Evaluation, Preclinical
  • Fluid Therapy / methods
  • Interleukin-6 / metabolism
  • Intestinal Obstruction / complications
  • Intestinal Obstruction / therapy*
  • Intestine, Small*
  • Isotonic Solutions / therapeutic use
  • Lung / drug effects
  • Male
  • NF-kappa B / metabolism
  • Neutrophils / drug effects
  • Oxidative Stress / drug effects
  • Pentoxifylline / therapeutic use*
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Resuscitation / methods
  • Ringer's Lactate
  • Saline Solution, Hypertonic / therapeutic use*
  • Shock, Hemorrhagic / etiology
  • Systemic Inflammatory Response Syndrome / etiology
  • Systemic Inflammatory Response Syndrome / prevention & control*

Substances

  • Cytokines
  • Interleukin-6
  • Isotonic Solutions
  • NF-kappa B
  • Ringer's Lactate
  • Saline Solution, Hypertonic
  • Pentoxifylline