Difference between revisions of "Montaigne 2010 Toxicol Appl Pharmacol"
(Created page with "{{Publication |title=Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R (2010) Stabilization of mitochondrial membrane potential p...") |
|||
| Line 2: | Line 2: | ||
|title=Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R (2010) Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart. Toxicol Appl. Pharmacol.244(3):300-307. | |title=Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R (2010) Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart. Toxicol Appl. Pharmacol.244(3):300-307. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/20096298 PMID:20096298] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/20096298 PMID:20096298] | ||
|authors=Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R | |authors=Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R | ||
|year=2010 | |year=2010 | ||
|journal=Toxicol Appl. Pharmacol | |journal=Toxicol. Appl. Pharmacol. | ||
|abstract=The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 microM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt(max) of 105+/-8 mN/s in control hearts vs. 49+/-7 mN/s in doxorubicin-treated hearts; p<0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0+/-0.2 in control hearts vs. 2.2+/-0.2 in doxorubicin-treated hearts; p<0.05) and cytochrome c oxidase kinetic activity (24+/-1 microM cytochrome c/min/mg in control hearts vs. 14+/-3 microM cytochrome c/min/mg in doxorubicin-treated hearts; p<0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity. | |abstract=The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 microM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt(max) of 105+/-8 mN/s in control hearts vs. 49+/-7 mN/s in doxorubicin-treated hearts; p<0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0+/-0.2 in control hearts vs. 2.2+/-0.2 in doxorubicin-treated hearts; p<0.05) and cytochrome c oxidase kinetic activity (24+/-1 microM cytochrome c/min/mg in control hearts vs. 14+/-3 microM cytochrome c/min/mg in doxorubicin-treated hearts; p<0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity. | ||
|keywords=mitochondria, oxidative phosphorylation, heart failure, anthracycline, NADH | |keywords=mitochondria, oxidative phosphorylation, heart failure, anthracycline, NADH | ||
Revision as of 10:57, 5 September 2011
| Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R (2010) Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart. Toxicol Appl. Pharmacol.244(3):300-307. |
Montaigne D, Marechal X, Baccouch R, Modine T, Preau S, Zannis K, Marchetti P, Lancel S, Neviere R (2010) Toxicol. Appl. Pharmacol.
Abstract: The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 microM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt(max) of 105+/-8 mN/s in control hearts vs. 49+/-7 mN/s in doxorubicin-treated hearts; p<0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0+/-0.2 in control hearts vs. 2.2+/-0.2 in doxorubicin-treated hearts; p<0.05) and cytochrome c oxidase kinetic activity (24+/-1 microM cytochrome c/min/mg in control hearts vs. 14+/-3 microM cytochrome c/min/mg in doxorubicin-treated hearts; p<0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity. • Keywords: mitochondria, oxidative phosphorylation, heart failure, anthracycline, NADH
• O2k-Network Lab: FR_Lille_Neviere R
Labels:
Organism: Rat
Tissue;cell: Cardiac Muscle"Cardiac Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Preparation: Permeabilized Cell or Tissue; Homogenate"Permeabilized Cell or Tissue; Homogenate" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
HRR: Oxygraph-2k
