title: Midazolam provides cytoprotective effect during corticosterone-induced damages in rat astrocytes by stimulating steroidogenesis.
abstract: Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. The cytoprotective effect of midazolam on brain astrocytes is poorly understood. This study aimed to investigate the cytoprotective effect of midazolam on astrocytes exposed to corticosterone, a stress-produced glucocorticoid. We found that midazolam stimulated pregnenolone and progesterone secretion in astrocytes in a dose-dependent manner. Midazolam protected astrocytes from corticosterone-induced damages in a dose-dependent manner. In addition, we demonstrated that progesterone reduced corticosterone-induced damages. Finally, we applied trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, to inhibit pregnenolone metabolism and found that pretreatment with trilostane significantly inhibited the cytoprotective effect of midazolam on corticosterone-induced cytotoxicity in rat astrocytes in a dose-dependent manner. Taken together, these results demonstrate that midazolam has cytoprotective effect on astrocytes. This is, at least partially, derived from midazolam-induced steroidogenesis including progesterone and downstream products in astrocytes. Our data provide new insights into the cytoprotective effect of midazolam.
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Guo
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Miao
authors.forename: Li-Na
authors.initials: LN
authors.lastname: An
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Wang
authors.forename: Ning-Ling
authors.initials: NL
authors.lastname: Pan
authors.forename: Ya-Qun
authors.initials: YQ
authors.lastname: Ma
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Mi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003345:Corticosterone / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008874:Midazolam / Q000494:pharmacology*; D011284:Pregnenolone / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006993:Hypnotics and Sedatives; D011374:Progesterone; D011284:Pregnenolone; D008874:Midazolam; D003345:Corticosterone