Topiramate Reduces Aortic Cross-Clamping-Induced Lung Injury in Male Rats.

Aysel Kurt,Erkan Cure,Hasan Turut,Levent Tumkaya,Medine Cumhur Cure,Yildiray Kalkan

doi:10.14712/18059694.2018.133

Abstract

Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R. A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group. Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group. During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.

Highlights

Pulmonary dysfunction is one of the problematic conditions developing after ischemic reperfusion (I/R) on account of lung transplantation [1], extracorporeal circulation operations [2, 3] after resuscitation for circulatory arrest [4] or severe hemorrhagic shock [5]
Tumor necrosis factor-alpha (TNF-α), MDA, MPO and ET-1 levels of the I/R group were found significantly higher than the controls and TPM-treatment group
In the TPM-treatment group, TNF-α, MDA, MPO and ET-1 levels were lower compared with the I/R group’s levels

Summary

Introduction

Pulmonary dysfunction is one of the problematic conditions developing after ischemic reperfusion (I/R) on account of lung transplantation [1], extracorporeal circulation operations [2, 3] after resuscitation for circulatory arrest [4] or severe hemorrhagic shock [5]. In its early stages, activated alveolar macrophages and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) increase, and reactive oxygen radicals (ROS) and later, in last stages of perfusion, activated neutrophils play crucial roles in this uncontrolled inflammation process [8, 9]. Endothelin-1 (ET-1), released from damaged endothelial cells, is another effective mediator causing vascular inflammation, cell proliferation, and fibrosis. This ET-1 plays a crucial role in the development of acute lung injury [11]. Results: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group’s lung tissue were significantly lower than for the I/R group. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced

Objectives

Methods

Results

Conclusion