Ebselen reduces inflammation and microvascular perfusion failure after blunt skeletal muscle injury of the rat

Abstract

Background: Soft tissue trauma induces an local inflammatory response and yields a microvascular perfusion failure due to trauma-induced oxidative stress. Using high-resolution multifluorescence microscopy, we herein report on the efficiency of treatment with the oxygen radical scavenger ebselen to improve compromised perfusion of traumatized muscle tissue and to minimize secondary tissue damage.

Methods: By using a pneumatically driven computer-controlled impact device, closed soft tissue trauma of the left hind limb was induced in pentobarbital-anesthetized rats that received either ebselen (30 mg/kg body weight, intraperitoneally) or equal volumes of the vehicle dimethyl sulfoxide (DMSO). In an additional series of animals, ebselen or DMSO were applied without soft tissue trauma.

Results: Ebselen restored microcirculatory impairment within the injured muscle, as given by values of nutritive perfusion (763 +/- 44 cm/cm2), nicotinamide adenine dinucleotide levels (56 +/- 3 aU) and inflammatory cell interaction (leukocytes: 226 +/- 31 mm(-2)) at 24 hours after trauma, being not different to those found in noninjured muscle tissue of controls. In contrast, skeletal muscle in DMSO-treated animals revealed persistent perfusion failure (564 +/- 32 cm/cm2) with tissue hypoxia (nicotinamide adenine dinucleotide 75 +/- 11 aU) and enhanced endothelial interaction of leukocytes (383 +/- 18 mm(-2)) at 24 hours after trauma.

Conclusions: Treatment of skeletal muscle soft tissue trauma with the glutathione peroxidase mimic ebselen is highly effective in restoration of disturbed microcirculation. Moreover, reduced inflammatory cell response helps to prevent leukocyte-dependent secondary tissue injury.