title: Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro.
abstract: Bile acid-induced lung injury has become an important topic for neonatologists after the discovery of a high incidence of infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis. To explore the molecular pathway of bile acid-induced lung injury, we investigated the cytotoxicity of the glycochenodeoxycholate (GCDC) to alveolar epithelial type II cells (AECII), as the main component of bile acid. The results demonstrated that glycochenodeoxycholate induced oxidative stress, mitochondrial damage, and increased caspase activity in the primary cultured AECII. Moreover, ROS scavengers and caspase inhibitors could rescue cell death induced by GCDC in rat AECII. Our results also indicated that GCDC inhibited AECII surfactant secretion. In conclusion, this study suggested that cell death prevention and cell therapy should be considered as therapeutic strategies for infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis.
authors.affiliation: Department of Pediatrics, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. huzx1@163.com
authors.forename: Hu
authors.initials: H
authors.lastname: Zhangxue
authors.forename: Gao
authors.initials: G
authors.lastname: Min
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jinning
authors.forename: Shi
authors.initials: S
authors.lastname: Yuan
authors.forename: Wang
authors.initials: W
authors.lastname: li
authors.forename: Song
authors.initials: S
authors.lastname: Huapei
authors.forename: Li
authors.initials: L
authors.lastname: Rui
authors.forename: Zeng
authors.initials: Z
authors.lastname: Chunyu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003902:Detergents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D003902:Detergents; D004791:Enzyme Inhibitors; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species; D005999:Glycochenodeoxycholic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D020169:Caspases