Elsevier

Burns

Volume 41, Issue 2, March 2015, Pages 379-385
Burns

Hydrogen-rich saline resuscitation alleviates inflammation induced by severe burn with delayed resuscitation

https://doi.org/10.1016/j.burns.2014.07.012Get rights and content

Abstract

Severe burns with delayed resuscitation are associated with high morbidity which is attributed to ischemia–reperfusion injury. This study was undertaken to investigate the effect of hydrogen-rich saline known as a significant selective antioxidant on the inflammatory reaction induced by severe burns with delayed resuscitation. By establishing the model of severe burns with delayed resuscitation in rats, we recorded improvement on the mortality, secretion of cytokines and reaction of oxidative stress of rats treated with hydrogen-rich saline. We found that resuscitation by hydrogen-rich saline alleviated inflammation significantly. We further detected the change of the key nuclear factor NF-κB contributed to inflammation. The expression of both NF-κB and phosphorylated NF-κB in rats having severe burns with delayed resuscitation by hydrogen-rich saline was lower than that in rats with delayed resuscitation with Ringers’ solution. Our data imply that hydrogen-rich saline significantly improves the inflammatory reaction in rats with severe burns with delayed resuscitation, possibly by inhibiting activation of NF-κB.

Introduction

Burn shock resuscitation is one of the key therapies in burn care, and severe burns with delayed resuscitation, defined as fluid resuscitation begun 6 h after injury, are associated with high morbidity and mortality [1], [2]. There is no effective treatment clinically, so it is urgent to solve this sophisticated problem [2].

Mounting evidence suggests that ischemia–reperfusion injury contributes to the tissue or organ damage, and the mainstay underlying mechanism is oxidative stress evoking inflammatory reaction. Persistent hypoperfusion resulted in hindrance of cellular energy metabolism which is involved in hypoxanthine as a substrate for xanthine oxidase. The process of reperfusion initiates the reaction between hypoxanthine and xanthine oxidase which produce abundant deleterious free radicals, for example, superoxide anion radical (O2−radical dot) and hydrogen peroxide (H2O2). Furthermore, adherent activated neutrophils are another important resource of free radicals in burn trauma. These free radicals contribute to additional tissue injury by upregulating the transcription factor nuclear factor kappa B (NF-κB) to promote transcription and translation of numerous inflammatory cytokines [3].

Recently, we found that hydrogen exhibited significant antioxidant effects with certain unique properties in varied disease models of oxidative stress. Research demonstrated that H2, acting as selective antioxidant is permeable to cell membranes and acts within cells [4], [5]. However, the effect of hydrogen on burn shock with delayed resuscitation has not been reported [4], [6], [7].

The purpose of the study was to determine whether hydrogen diminishes the inflammatory reaction induced by severe burns with delayed resuscitation in a rat model that is of particular clinical significance when discussing the treatment for severe burns with delayed resuscitation.

Section snippets

Animals

All animal experimental procedures and protocols in this study were carried out according to the National Institutes of Health guidelines on the use of experimental animals and were approved by Institutional Animal Care and Use Committees (IACUC) at the Third Military Medical University. Male Wistar rats weighing 200–250 g were purchased from the Experimental Animal Department of the Third Military Medical University, Chongqing, China. All animals were maintained under specific pathogen-free

Resuscitation by hydrogen-rich saline reduces mortality in burns with delayed resuscitation

To identify the effect of hydrogen-rich saline on delayed resuscitation, we first monitored the rat survival time daily (Fig. 1). Rats with resuscitation immediately after burns were considered as control for which the average survival time was 8 days. All rats with delayed resuscitation by Ringer solution died within 5 days and the average survival time was only 2 days. By contrast, delayed resuscitation by hydrogen-rich saline reduced mortality significantly and the average survival time was

Discussion

Severe burns with delayed resuscitation are a distressing problem and its treatment often proves frustrating for clinicians which is associated with high morbidity and mortality. Reducing the damage by oxidative stress is one of the current main treatments. Hydrogen-rich saline is proved in various disease models to be better in improving damage induced by oxidative stress for clearing the free radicals selectively [7], [8], [9]. Here, we show hydrogen-rich saline prolonged survival, decreased

Conflict of interest statement

None declared.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81101427). The authors acknowledge the kind assistance of Professor Wujun (Institute of Burn Research, Southwest Hospital, Third Military Medical University, China) for providing the experimental laboratory.

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These authors contributed equally to this work.

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