title: Etomidate induces cytotoxic effects and gene expression in a murine leukemia macrophage cell line (RAW264.7).
abstract: Etomidate is an important tool in the arsenal of the emergency physician, and it has been used in a variety of scenarios for both intubation and procedural sedation. In the present study, we investigated the cytotoxicity of etomidate including induction of apoptosis, and levels of protein and gene expressions associated with apoptotic cell death in murine leukemia RAW264.7 cells in vitro. Cytotoxic and apoptotic responses to etomidate of RAW264.7 cells, including cell morphological changes and cell viability were examined and measured by phase-contrast microscopy and flow cytometric assay, respectively. Results indicated that etomidate increased apoptotic cell morphological changes and reduced cell viability in RAW264.7 cells. 4',6-Diamidino-2-phenylindole (DAPI) staining also showed that etomidate induced the formation of apoptotic bodies, a characteristic of apoptosis. Results from Western blotting indicated that etomidate enhanced the levels of cytochrome c, apoptosis-inducing factor (AIF), endonuclease G (Endo G), caspase-9, caspase-3 active form and Bax proteins, but it inhibited the expression of Bcl-xl, leading to apoptosis. DNA microarray assay indicated that etomidate increased the expression of 17 genes (LOC676175; Gm14636; 2810021G02Rik; Iltifb; Olfr1167; Ttc30b; Olfr766; Gas5; Rgs1; LOC280487; V1rd4; Hist1h2bc; V1rj3; Gm10366; Olfr192; Gm10002 and Cspp1) and reduced the expression of 15 genes: (Gm10152; Gm5334; Olfr216; Lcn9; Gm10683; Gm5100; Tdgf1; Cypt2; Gm5595; 1700018F24Rik; Gm10417; Maml2; Olfr591; Trdn and Apol7c). In conclusion, etomidate induced cytotoxic and apoptotic effects the in murine leukemia RAW264.7 cells in vitro.
authors: Department of Anesthesiology, China Medical University Hospital, and Department of Pharmacology, School of Pharmacy, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC.
authors: Rick Sai-Chuen
authors: RS
authors: Wu
authors: King-Chuen
authors: KC
authors: Wu
authors: Jai-Sing
authors: JS
authors: Yang
authors: Shang-Ming
authors: SM
authors: Chiou
authors: Chun-Shu
authors: CS
authors: Yu
authors: Shu-Jen
authors: SJ
authors: Chang
authors: Fu-Shin
authors: FS
authors: Chueh
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005045:Etomidate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice
chemical_list: D005045:Etomidate