title: Alcoholism and alcohol abstinence: N-acetylcysteine to improve energy expenditure, myocardial oxidative stress, and energy metabolism in alcoholic heart disease.
abstract: Alcoholism has been associated with a wide range of pathologic conditions, including alcoholic heart disease (AHD). Because AHD may be associated with oxidative stress, antioxidant compounds, such as N-acetylcysteine (NAC) could be useful to control the damage done by alcohol (ethanol) consumption. To investigate the NAC effects on alcoholism and alcohol abstinence, initially, 30 male Wistar rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol-exposure, (E) group was divided into four subgroups (N=6/group):(E-E) continued drinking 30% ethanol-solution; (E-NAC) drinking ethanol-solution containing 2g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution of 2g/L NAC. After 15 days of the E-group division, E-E rats had lower body weight and feed efficiency, as well as higher energy-expenditure resting metabolic rate (RMR)/body weight and VO(2) consumption/surface area. These calorimetric changes were reflected on the cardiac tissue. E-E rats had higher heart weight/body weight ratio and myocardial lipid hydroperoxide (LH), indicating AHD with hypertrophy and oxidative stress. Myocardial superoxide dismutase was higher, whereas glutathione-peroxidase (GSH-peroxidase) was lower in E-E rats than in C. The higher myocardial hydroxyacyl coenzyme-A dehydrogenase (OHADH), OHADH/citrate synthase (CS), and lactate dehydrogenase (LDH)/CS in E-E rats indicated higher fatty acid degradation relative to aerobic metabolism predisposing the lipotoxicity. AB rats had lower RMR/body weight than E-E, normalized myocardial oxidative stress, and energy metabolism. E-NAC and AB-NAC had lower RMR/body weight, myocardial LH, LDH/CS, and higher GSH-peroxidase than E-E and AB, respectively, demonstrating lower oxidative stress and higher myocardial carbohydrate oxidation. In conclusion, the present study brought new insights on alcohol consumption and AHD because ethanol-exposure enhanced energy-expenditure and induced a number of calorimetric changes, which were reflected in body weight and myocardial lipotoxicity. NAC preventing ethanol-induced calorimetric changes and reducing myocardial oxidative stress enhanced carbohydrate oxidation, thus optimizing myocardial energy metabolism in both alcoholic and abstinence condition.
authors.affiliation: Department of Clinical and Cardiology, School of Medicine, São Paulo State University, Botucatu, São Paulo, Brazil.
authors.forename: Fábio Rodrigues Ferreira
authors.initials: FR
authors.lastname: Seiva
authors.forename: Juliana Fujihara
authors.initials: JF
authors.lastname: Amauchi
authors.forename: Katiucha Karolina Ribeiro
authors.initials: KK
authors.lastname: Rocha
authors.forename: Geovana Xavier
authors.initials: GX
authors.lastname: Ebaid
authors.forename: Gisele
authors.initials: G
authors.lastname: Souza
authors.forename: Ana Angélica Henrique
authors.initials: AA
authors.lastname: Fernandes
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Cataneo
authors.forename: Ethel Lourenzi Barbosa
authors.initials: EL
authors.lastname: Novelli
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D006331:Heart Diseases / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D013695:Temperance
chemical_list: D000111:Acetylcysteine