Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Biomed Res Int. 2016:2016:5302069. doi: 10.1155/2016/5302069. Epub 2016 Jul 31.

Abstract

Objectives. The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγ plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage. Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγ inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n = 8 rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey's testing were used for statistical analysis. Results. Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1β levels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury. Conclusion. These results suggest that PPARγ might play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Cyclohexanes / pharmacology*
  • Lung Injury / etiology
  • Lung Injury / metabolism
  • Lung Injury / physiopathology
  • Lung Injury / prevention & control*
  • Male
  • Maraviroc
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Hemorrhagic / complications
  • Shock, Hemorrhagic / drug therapy*
  • Shock, Hemorrhagic / metabolism
  • Shock, Hemorrhagic / physiopathology
  • Triazoles / pharmacology*
  • Wounds and Injuries / complications
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / physiopathology

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Cyclohexanes
  • Triazoles
  • Maraviroc