Affiliations 

  • 1 Post-Doctoral Innovation Site, Jinan University Affiliation, Yuanzhi Health-tech Inc., Hengqin District, Zhuhai 519000, Guangdong, China; Kesi (Shandong) Innovation Service Inc., heze modern medical port, Mudan district, Heze 274009, Shandong, China; Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
  • 2 Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
  • 3 Post-Doctoral Innovation Site, Jinan University Affiliation, Yuanzhi Health-tech Inc., Hengqin District, Zhuhai 519000, Guangdong, China; Kesi (Shandong) Innovation Service Inc., heze modern medical port, Mudan district, Heze 274009, Shandong, China; Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia. Electronic address: uscnwt@163.com
Int Immunopharmacol, 2023 Aug;121:110482.
PMID: 37364330 DOI: 10.1016/j.intimp.2023.110482

Abstract

Salbutamol, which consists of an R-isomer and S-isomer, is an effective and widely used β2 adrenoreceptor agonist that may possess anti-inflammatory properties in addition to its bronchodilator activity. Whether the salbutamol R-isomer has advantages over its racemic mixture and effectiveness in treating endotoxemia and endotoxin-induced lung injury has not been well studied. In this study, we investigated the preventive and therapeutic effects of R-salbutamol (R-sal), S-salbutamol (S-sal), and their racemic mixture (Rac-sal) on a mouse model of lipopolysaccharide (LPS)-induced endotoxemia. Dexamethasone (Dex) was used for comparison. The results showed that R-sal markedly improved the 7-day survival rate of endotoxic mice when administered before and after LPS treatment. Dex was toxic and accelerated the death of endotoxic mice when administered before LPS injection. Histological examination of the lungs revealed that the LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa, and congestion. R-sal pre-treatment effectively inhibited these changes, accompanied by markedly reduced lung myeloperoxidase levels, serum cytokine levels, and lactate release, significant restoration of lymphocyte count, and reduction of monocyte count. This may have occurred through inhibition of M1 macrophage inflammatory responses by enhancement of β-arrestin2 expression and suppression of NF-κB activation. Rac-sal exhibited diminished effects compared to that of R-sal, while S-sal showed enhanced release of some inflammatory cytokines. In addition, R-sal pre-treatment showed a better improvement in prognostic pulmonary function on day 4 compared to that by Rac-sal. Collectively, our results indicate the potential benefits of R-sal in regulating inflammatory responses to endotoxemia and endotoxin-induced lung injury.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.