title: Effects of purple grape juice in the redox-sensitive modulation of right ventricular remodeling in a pulmonary arterial hypertension model.
abstract: The effects of purple grape juice (PGJ) pretreatment in signaling proteins involved in cardiac remodeling in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) were investigated. Male Wistar rats (control, MCT, PGJ, and MCT + PGJ groups) were treated for 6 weeks with water or PGJ (10 mL·kg(-1)·d(-1)) by gavage. In the third week, they were administered a single dose of MCT (60 mg/kg i.p.). Pulmonary vascular resistance was determined by echocardiography, and hemodynamic analysis was performed in the right ventricle (RV). Hydrogen peroxide (H2O2) concentration and lipid peroxidation were quantified and thioredoxin-1 (Trx-1), p-ERK1/2/ERK1/2, p-Akt/Akt, p-JNK/JNK, and cleaved caspase-3 were detected at RV by Western blot. Pretreatment with PGJ attenuated pulmonary vascular resistance and improved hemodynamic parameters in MCT-induced PAH. PGJ and MCT groups exhibited increased H2O2 levels, which were reduced to baseline in MCT + PGJ. ERK1/2 phosphorylation showed the same profile of H2O2 changes. No changes in p-JNK/JNK and p-Akt/Akt expressions were found. An enhanced cleaved caspase-3 immunodetection was induced by the model, which was reversed in the MCT + PGJ group and associated with increased Trx-1 and reduced lipid peroxidation. Improvement in functional parameters mediated by PGJ pretreatment may be associated with the induction of Trx-1, influencing the expression of proteins involved in RV remodeling.
authors.affiliation: Programa de Pós-Graduação em Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mosele
authors.forename: Angela M V
authors.initials: AM
authors.lastname: Tavares
authors.forename: Rafael
authors.initials: R
authors.lastname: Colombo
authors.forename: Rafaela
authors.initials: R
authors.lastname: Caron-Lienert
authors.forename: Alex S R
authors.initials: AS
authors.lastname: Araujo
authors.forename: Maria F
authors.initials: MF
authors.lastname: Ribeiro
authors.forename: Adriane
authors.initials: A
authors.lastname: Belló-Klein
mesh_terms: D000818:Animals; D001628:Beverages; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D065627:Familial Primary Pulmonary Hypertension; D006861:Hydrogen Peroxide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*; D027843:Vitis / Q000737:chemistry*
chemical_list: D013879:Thioredoxins; D016686:Monocrotaline; D006861:Hydrogen Peroxide; D053148:Caspase 3