title: Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells.
abstract: Patients with diabetes mellitus, particularly those with cardiovascular complications, have increased risk of mortality when subject to anesthetics and surgery, compared with non-diabetic patients. Anesthetics may exert pressure on the cardiovascular system of diabetic patients, directly or by aggravating pre-existing cardiovascular complications. Advanced glycation end products (AGEs) are extremely accumulated in diabetes mellitus, and are confirmed to play an important role in the pathogenesis of diabetic microvascular and macrovascular complications. The purpose of the present study was to investigate the regulatory role of etomidate, which is widely used as intravenous general anesthetics, on the viability and apoptosis of human endothelial Eahy926 cells, in the presence of AGEs. The results demonstrated that etomidate and Glu-BSA (one type of AGE) synergistically reduced the human endothelial Eahy926 cell viability and induced cell apoptosis. In addition, western blot assay of apoptosis-associated molecules indicated that both agents synergistically upregulated the cytochrome c release, activated the apoptosis executor, caspase 3, and promoted the poly-ADP-ribose polymerase (PARP) lysis. Further results confirmed that the two agents synergistically promoted oxidative stress by decreasing mitochondrial respiratory chain complex IV and mitochondrial membrane potential (MMP), while upregulating reactive oxygen species (ROS) and mitochondrial superoxide. In conclusion, the results presented in this study offer a novel insight into the mechanisms of endothelial cell apoptosis in response to etomidate in the presence of AGEs. These results suggest that oxidative stress has important role in the synergistic promotion of apoptosis by etomidate and AGEs in endothelial Eahy926 cells.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Inner Mongolia Medical University, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Arong
authors.initials: A
authors.lastname: Jin
authors.forename: Min
authors.initials: M
authors.lastname: An
authors.forename: Yumei
authors.initials: Y
authors.lastname: Ding
authors.forename: Ya
authors.initials: Y
authors.lastname: Tuo
authors.forename: Yi
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects*; D005045:Etomidate / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology / Q000633:toxicity*; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases
chemical_list: D018686:Anesthetics, Intravenous; D017127:Glycation End Products, Advanced; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D005045:Etomidate