Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo.
OBJECTIVE
To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine.


METHODS
Prospective, randomized, controlled study.


METHODS
Research laboratory.


METHODS
Sprague Dawley rats.


METHODS
Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine).


RESULTS
In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Δψm), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorβ, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and PaCO2 were significantly increased, and oxygen (PaO2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure.


CONCLUSIONS
Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar epithelial cell from bilirubin-induced injury. Dexmedetomidine may be a good choice of anesthetic/sedative for patients with chronic liver disease during the perioperative period.
1Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China. 2Section of Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom.
Jian
J
Cui
Hailin
H
Zhao
Bin
B
Yi
Jing
J
Zeng
Kaizhi
K
Lu
Daqing
D
Ma
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002453:Cell Cycle; D045304:Cytochromes c / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D006932:Hyperbilirubinemia / Q000150:complications; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000293:injuries / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D058669:Adrenergic alpha-2 Receptor Antagonists; D020927:Dexmedetomidine; D045304:Cytochromes c