Rescuable effect of R-salbutamol in LPS-induced immune dysfunction of sepsis

Author:

Beng HuiminORCID,Wang Shanping,Hu Junhua,Liang Xinglong,Qin Haolong,Tan Wen

Abstract

AbstractSepsis is a severe life-threatening condition caused by a dysregulated host response to infection. So far, there are no pharmacotherapies to stop sepsis. Salbutamol, an commonly used β2-adrenoreceptor agonist, has found to be potential in regulating immune response dysfunction and exert anti-inflammatory effect. However, salbutamol exists two isomers. R-isomer exhibits the therapeutic effect and clinical benefit, while S-isomer proves to be detrimental rather than benign. So, in this study, we investigated the preventive and therapeutic effect of R-salbutamol (R-sal), S-salbutamol (S-sal) or racemic mixture in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Dexamethasone (Dex) was set as comparison. The results showed that R-sal markedly improved seven-day survival rate of septic mice both administered before or after LPS. Whereas Dex showed toxic and accelerated the death of septic mice when given before LPS injection. Lung histological examination and lung function assay revealed that LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa and congestion, and decreased minute volume in septic mice. R-sal pretreatment efficiently inhibited these changes, accompanying by markedly reduced lung MPO level, serum cytokines levels and lactate release and significantly restored the lymphocytes and suppressed the percentage of monocytes. Racemic mixture exhibited diminished effects while S-sal showed enhanced cytokines release. In addition, R-sal pretreatment showed a better improvement in prognostic pulmonary function at day4 in survived mice than that of Rac-sal. Collectively, our results indicate the potential benefit of R-sal for sepsis and sepsis-induced lung injury.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3