title: Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats.
abstract: Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E2 modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5g/kg i.v.) 30-min after E2 (1μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dtmax) and systolic (SBP) and diastolic (DBP) blood pressures in E2-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E2 promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E2 for specific medical conditions.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: mahelm@hotmail.com.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: abdelrahmana@ecu.edu.
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004958:Estradiol / Q000633:toxicity*; D000431:Ethanol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000431:Ethanol; D004958:Estradiol; C579097:Dapk3 protein, rat; D064550:Death-Associated Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Estrogen; Ethanol; Extracellular signal-regulated kinases; LV dysfunction; Male rats; Oxidative stress