title: Pretreatment with low dose etomidate prevents etomidate-induced rat adrenal insufficiency by regulating oxidative stress-related MAPKs and apoptosis.
abstract: Etomidate is frequently used as an anesthetic and sedation agent in the clinic setting. This study determined that a low-dose pre-infusion followed by a continuous dose infusion of etomidate could reduce etomidate-induced adrenal gland insufficiency. Sixty adult male Wistar rats were used, with six rats per group. Based on preliminary experiments, 0.6mg/kg etomidate was selected as the low dose for this study. Oxidative stress and apoptosis-related proteins in the adrenal glands were assayed using Western blot, and serum levels of CORT and 11β-hydroxylase were detected using ELISA. Pretreatment with a single bolus of low dose etomidate significantly increased the levels of CORT and 11β-hydroxylase as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathioneperoxidase (GPx) in the adrenal glands, but reduced nitric oxide (NO) production when compared to the positive group. Furthermore, Western blot data showed that pretreatment with low dose etomidate increased extracellular signal-regulated kinase1/2 (ERK1/2), CREB and bcl-2 activation, but suppressed the p-p38, c-JunN-terminal kinase (JNK), inducible NO synthase (iNOS), cleaved-caspase3, cleaved-poly-ADP-ribose polymerase (PARP), bax, and AKT activation. The ERK inhibitor PD98059 and the p38MAPK inhibitor SB203580 abolished the protective effect of low dose etomidate pretreatment. These data demonstrated that pretreatment with low dose etomidate attenuated etomidate-induced adrenal insufficiency to rat adrenal glands. Oxidative stress-related MAPKs and apoptosis proteins might be responsible for mediating the etomidate preconditioning effect in rats.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116027, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116027, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116027, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Han
authors.affiliation: Laboratory of Molecular Biology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116027, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116027, China. Electronic address: jyxiong0639@163.com.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Xiong
mesh_terms: D000309:Adrenal Insufficiency / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020928:Mitogen-Activated Protein Kinases; D005045:Etomidate
keywords: AKT; Adrenal gland insufficiency; Etomidate; MAPK; Oxidative stress