@article {2650, title = {Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation}, journal = {Biochemical and Biophysical Research Communications}, volume = {389}, number = {1}, year = {2009}, note = {ISI Document Delivery No.: 555SMTimes Cited: 4Cited Reference Count: 26Wang, Baohua Shravah, Jayant Luo, Honglin Raedschelders, Koen Chen, David D. Y. Ansley, David M.}, month = {Nov}, pages = {105-111}, type = {Article}, abstract = {

Propofol is a widely used intravenous anesthetic agent with antioxidant properties secondary to its phenol based chemical structure. Treatment with propofol has been found to attenuate oxidative stress and prevent ischemia/reperfusion injury in rat heart. Here, we report that propofol protects cardiac H9c2 cells from hydrogen peroxide (H2O2)-induced injury by triggering the activation of Akt and a parallel up-regulation of Bcl-2. We show that pretreatment with propofol significantly protects against H2O2-induced injury. We further demonstrate that propofol activates the PI3K-Akt signaling pathway. The protective effect of propofol on H2O2-induced injury is reversed by PI3K inhibitor wortmannin, which effectively suppresses propofol-induced activation of Akt, up-regulation of Bcl-2, and protection from apoptosis. Collectively, our results reveal a new mechanism by which propofol inhibits H2O2-induced injury in cardiac H9c2 cells, supporting a potential application of propofol as a preemptive cardioprotectant in clinical settings such as coronary bypass surgery. (C) 2009 Elsevier Inc. All rights reserved.

}, keywords = {15-F-2T-ISOPROSTANE FORMATION, Akt, antioxidant capacity, apoptosis, Bcl-2, CARDIOMYOCYTES, ENDOTHELIAL-CELLS, H9c2 cells, INJURY, KINASE-C, OXIDATIVE STRESS, Propofol, RAT-HEART, REDUCES APOPTOSIS, REPERFUSION, SENSITIVITY, SURVIVAL}, isbn = {0006-291X}, doi = {doi: 10.1016/j.bbrc.2009.08.097}, url = {://000274534900020}, author = {Wang, B. H. and Shravah, J. and Luo, H. L. and Raedschelders, K. and Chen, D. D. Y. and Ansley, D. M.} } @article {2568, title = {Target-achieved propofol concentration during on-pump cardiac surgery: a pilot dose-finding study}, journal = {Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie}, volume = {56}, number = {9}, year = {2009}, note = {ISI Document Delivery No.: 486HMTimes Cited: 0Cited Reference Count: 45Raedschelders, Koen Hui, Yu Laferlita, Bradley Luo, Tao Zhang, Hong Chen, David D. Y. Ansley, David M.}, month = {Sep}, pages = {658-666}, type = {Article}, abstract = {Propofol concentrations that produce laboratory-based cardioprotective effects are generally greater than those produced under routine anesthesia during cardiac surgery. It is unknown whether experimental cardioprotective propofol concentrations can routinely be achieved during cardiopulmonary bypass (CPB) using continuous infusion. Twenty-four patients scheduled for primary aortocoronary bypass grafting with CPB were allocated to receive one of three propofol infusion rates; 50, 100, or 150 mu g center dot A kg(-1) center dot A min(-1) in an open-label pilot study. Data were described using a line of best fit to derive an experimental clinical maneuver predicted to produce a whole blood concentration of 5 mu g center dot A mL(-1) at reperfusion. A predetermined interim analysis of 30 patients who were receiving the derived maneuver in an ongoing study was used to evaluate the maneuver. Cardiac index (CI), systemic vascular resistance index (SVRI), and left ventricular stroke work index (LVSWI) were recorded. The infusion rate-concentration curve had an equation of y = 0.215e (0.0279x) , where y represents the whole blood concentration and x represents the infusion rate (r (2) = 0.781). The predicted infusion rate to achieve a mean concentration of 5 mu g center dot A mL(-1) was 113 mu g center dot A kg(-1) center dot A min(-1). The nearest practical rate is 120 mu g center dot A kg(-1) center dot A min(-1), producing a concentration of 5.39 (1.45) mu g center dot A mL(-1). The values for CI, SVRI, and LVSWI were similar between groups at corresponding time periods. An infusion rate of 120 mu g center dot A kg(-1) center dot A min(-1) is clinically practical and capable of achieving experimental cardioprotective propofol concentrations at reperfusion.}, keywords = {ANESTHETICS, antioxidant capacity, cell, CORONARY SURGERY, ISCHEMIA-REPERFUSION INJURY, K-ATP CHANNELS, MYOCARDIAL-FUNCTION, NORMOTHERMIC CARDIOPULMONARY BYPASS, PERMEABILITY TRANSITION, PLASMA-CONCENTRATIONS, RAT HEARTS, VOLATILE}, isbn = {0832-610X}, url = {://000269186900005}, author = {Raedschelders, K. and Hui, Y. and Laferlita, B. and Luo, T. and Zhang, H. and Chen, D. D. Y. and Ansley, D. M.} } @article {1204, title = {Synthesis and characterization of dual function vanadyl, gallium and indium curcumin complexes for medicinal applications}, journal = {Journal of Inorganic Biochemistry}, volume = {99}, number = {11}, year = {2005}, note = {ISI Document Delivery No.: 984RUTimes Cited: 22Cited Reference Count: 41}, month = {Nov}, pages = {2217-2225}, type = {Article}, abstract = {Novel bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione (curcumin) complexes with the formula, ML3, where M is Ga(III) or In(III), or of the formula, ML2 where M is [Vo](2+), have been synthesized and characterized by mass spectrometry, infrared and absorption spectroscopies, and elemental analysis. A new ligand, bis[4-acetyl-3-hydroxyphenyl]-1,6-heptadiene-3,5-dione (diacetylbisdemethoxycurcumin, DABC) was similarly characterized; an X-ray structure analysis was performed. Vanadyl complexes tested in an acute i.p. testing protocol in STZ-diabetic rats showed a lack of insulin enhancing potential. Vanadyl complexes were, however, more cytotoxic than were the ligands alone in standard MTT (3-[4,5-dimethylthiazole-2-yl]ate, -2.5-diphenyl-tetrazolium bromide) cytotoxicity testing, using mouse lymphoma cells. With the exception of DABC, that was not different from VO(DABC)(2), the complexes were not significantly different from one another, with IC50 values in the 5-10 mu M range. Gallium and indium curcumin complexes had IC50 values in the same 5-10 mu M range; whereas Ga(DAC)(3) and In(DAC)(3) (where DAC = diacetylcurcumin) were much less cytotoxiC (IC50 = 20-30 mu M). Antioxidant capacity was decreased in VO(DAC)(2), Ga(DAC)(3), and In(DAC)(3),, compared to vanadyl, gallium and indium curcumin, corroborating the importance of curcumin{\textquoteright}s free phenolic OH groups for scavenging oxidants, and correlated with reduced cytotoxic potential. (c) 2005 Elsevier Inc. All rights reserved.}, keywords = {ANALOGS, antioxidant capacity, ANTIOXIDANT MECHANISM, ANTITUMOR ACTIVITY, BINDING, COORDINATION CHEMISTRY, curcumin, cytotoxicity, DERIVATIVES, diacetylcurcumin, gallium, GROUP, indium, INSULIN MIMICS, MANGANESE COMPLEXES, RADICAL SCAVENGING ABILITY, TOXICITY, VANADIUM}, isbn = {0162-0134}, url = {://000233322800012}, author = {Mohammadi, K. and Thompson, K. H. and Patrick, B. O. and Storr, T. and Martins, C. and Polishchuk, E. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris} }