Dexmedetomidine against intestinal ischemia/reperfusion injury: A systematic review and meta-analysis of preclinical studies

Min Hou; Feng Chen; Yao He; Zhiguo Tan; Xuena Han; Yajing Shi; Yunpeng Xu; Yufang Leng

doi:10.1016/j.ejphar.2023.176090

Dexmedetomidine against intestinal ischemia/reperfusion injury: A systematic review and meta-analysis of preclinical studies

Eur J Pharmacol. 2023 Nov 15:959:176090. doi: 10.1016/j.ejphar.2023.176090. Epub 2023 Sep 29.

Authors

Min Hou¹, Feng Chen², Yao He³, Zhiguo Tan⁴, Xuena Han⁵, Yajing Shi⁶, Yunpeng Xu⁷, Yufang Leng⁸

Affiliations

¹ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: hmrr0408@163.com.
² The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: chenf20@lzu.edu.cn.
³ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: hey2021@lzu.edu.cn.
⁴ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: 879280496@qq.com.
⁵ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: hanxuenatianjin@163.com.
⁶ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: shiyj20@lzu.edu.cn.
⁷ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: 839943643@qq.com.
⁸ The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China; Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China. Electronic address: lengyf@lzu.edu.cn.

PMID: 37778612
DOI: 10.1016/j.ejphar.2023.176090

Abstract

Background: Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α₂-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.

Methods: Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.

Results: There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).

Conclusions: DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.

Keywords: Dexmedetomidine; Intestinal ischemia/reperfusion injury; Meta-analysis; Preclinical studies; Systematic review.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Adrenergic alpha-2 Receptor Agonists / therapeutic use
Animals
Dexmedetomidine* / pharmacology
Dexmedetomidine* / therapeutic use
Inflammation / drug therapy
Ischemia / drug therapy
Rats
Rats, Sprague-Dawley
Reperfusion Injury* / pathology

Substances

Dexmedetomidine
Adrenergic alpha-2 Receptor Agonists