Edaravone attenuates lung injury in a hind limb ischemia-reperfusion rat model: A histological, immunohistochemical and biochemical study

Ann Anat. 2020 Mar:228:151433. doi: 10.1016/j.aanat.2019.151433. Epub 2019 Oct 31.

Abstract

Edaravone is a potent free radical scavenger that has a promising role in combating many acute lung injuries. Ischemia/reperfusion process is a serious condition that may lead to multiple organ dysfunctions. This work was designed to investigate novel mechanisms underlying ischemia/reperfusion-induced lung injury and to evaluate the protective role of edaravone. Thirty adult male rats were divided into three experimental groups; operated with no ischemia (Sham-group), ischemia/reperfusion (I/R) group and edaravone-I/R group. Hind limb ischemia was carried out by clamping the femoral artery. After two hours of ischemia for the hind limb, the rat underwent 24h of reperfusion. Rats in the edaravone-I/R group received edaravone (3mg/kg), 30min before induction of ischemia. At the end of the I/R trial, specimens from the lungs were processed for histological, immunohistochemical, enzyme assay, and RT-qPCR studies. Specimens from I/R group showed focal disruption of the alveolar architecture. Extensive mononuclear cellular infiltration particularly with neutrophils and dilated congested blood capillaries were observed. A significant increase in iNOS, NF-κB, and COX-2 immunoreaction was detected and confirmed by RT-qPCR. Ultrastructural examination showed RBCs and fluid inside alveoli, cellular infiltration, and vacuolations of the inter-alveolar septum. In addition to the presence of extravasated neutrophils and RBCs within the inter-alveolar septum. In contrast, minimal changes were observed in rats which received edaravone before the onset of the ischemia. It could be concluded that edaravone exerted a potent protective effect against lung injury induced by a hind limb I/R in rats through its antioxidant and anti-inflammatory activities.

Keywords: Edaravone; Electron microscopy; Ischemia/reperfusion; Lung; RT-qPCR.

MeSH terms

  • Animals
  • Biochemical Phenomena / physiology
  • Disease Models, Animal
  • Edaravone / therapeutic use*
  • Electron Transport Complex IV / analysis
  • Electron Transport Complex IV / genetics
  • Hindlimb / blood supply
  • Immunohistochemistry
  • Lung / enzymology
  • Lung / pathology
  • Lung / ultrastructure
  • Lung Injury / drug therapy*
  • Lung Injury / etiology
  • Lung Injury / pathology
  • Male
  • Microscopy, Electron, Transmission
  • NF-kappa B / analysis
  • NF-kappa B / genetics
  • Neuroprotective Agents / therapeutic use*
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / genetics
  • Oxidative Stress
  • Peroxidase / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Electron Transport Complex IV
  • Edaravone