Patrick Türck1, Schauana Fraga2, Isadora Salvador2, Cristina Campos-Carraro2, Denise Lacerda3, Alan Bahr2, Vanessa Ortiz2, Alexandre Hickmann2, Mariana Koetz4, Adriane Belló-Klein2, Amélia Henriques4, Fabiana Agostini5, Alex Sander da Rosa Araujo6. 1. Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Brazil. Electronic address: p.turck@gmail.com. 2. Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Brazil. 3. Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Brazil. 4. Postgraduate Program in Pharmaceutical Sciences, Pharmacy College, Federal University of Rio Grande do Sul, Brazil. 5. Postgraduate Program at Biosciences and Rehabilitation, Centro Universitário Metodista-IPA, Porto Alegre, Brazil. 6. Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Brazil; Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Brazil.
Abstract
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a condition characterized by an increased resistance of pulmonary vasculature, culminating in an increase in pulmonary pressure. This process involves disturbances in lung redox homeostasis, causing progressive right heart failure. In this context, the use of natural antioxidants, such as those found in blueberries, may represent a therapeutic approach. The aim of this study was to evaluate the effect of blueberry extract (BB) on functional parameters and oxidative stress levels in rat lungs with induced PAH. METHODS: Forty-eight male Wistar rats (weighing 200 ± 20 g) were randomized into five groups: control, monocrotaline, monocrotaline + BB 50, monocrotaline + BB 100, and monocrotaline + BB 200. PAH was induced by the administration of monocrotaline (60 mg/kg, intraperitoneal). Rats were treated with BB at doses of 50, 100, and 200 mg/kg via gavage for 5 wk (2 wk before monocrotaline and 3 wk after monocrotaline injection). At day 35, rats were submitted to echocardiography and catheterization. They were then sacrificed and lungs were harvested for biochemical analyses. RESULTS: BB increased the E/A ratio of blood flow across the tricuspid valve and tricuspid annular phase systolic excursion, as wells as decreased the mean pulmonary artery pressure of animals compared with the PAH group. Moreover, BB decreased total reactive species concentration and lipid oxidation, reduced activity of nicotinamide adenine dinucleotide phosphate oxidase and expression of xanthine oxidase, increased the activity of superoxide dismutase and restored sulfhydryl content in the animal lungs compared with those in the PAH group. Additionally, BB restored expression of the antioxidant transcriptional factor Nrf2 in the lungs of the animal subjects. Finally, BB normalized the endothelin receptor (ETA/ETB) expression ratio in the animal lungs, which were increased in the PAH group. CONCLUSION: Intervention with BB mitigated functional PAH outcomes through improvement of the pulmonary redox state. Our results provide a basis for future research on natural antioxidant interventions as a novel treatment strategy in PAH.
OBJECTIVES:Pulmonary arterial hypertension (PAH) is a condition characterized by an increased resistance of pulmonary vasculature, culminating in an increase in pulmonary pressure. This process involves disturbances in lung redox homeostasis, causing progressive right heart failure. In this context, the use of natural antioxidants, such as those found in blueberries, may represent a therapeutic approach. The aim of this study was to evaluate the effect of blueberry extract (BB) on functional parameters and oxidative stress levels in rat lungs with induced PAH. METHODS: Forty-eight male Wistar rats (weighing 200 ± 20 g) were randomized into five groups: control, monocrotaline, monocrotaline + BB 50, monocrotaline + BB 100, and monocrotaline + BB 200. PAH was induced by the administration of monocrotaline (60 mg/kg, intraperitoneal). Rats were treated with BB at doses of 50, 100, and 200 mg/kg via gavage for 5 wk (2 wk before monocrotaline and 3 wk after monocrotaline injection). At day 35, rats were submitted to echocardiography and catheterization. They were then sacrificed and lungs were harvested for biochemical analyses. RESULTS: BB increased the E/A ratio of blood flow across the tricuspid valve and tricuspid annular phase systolic excursion, as wells as decreased the mean pulmonary artery pressure of animals compared with the PAH group. Moreover, BB decreased total reactive species concentration and lipid oxidation, reduced activity of nicotinamide adenine dinucleotide phosphate oxidase and expression of xanthine oxidase, increased the activity of superoxide dismutase and restored sulfhydryl content in the animal lungs compared with those in the PAH group. Additionally, BB restored expression of the antioxidant transcriptional factor Nrf2 in the lungs of the animal subjects. Finally, BB normalized the endothelin receptor (ETA/ETB) expression ratio in the animal lungs, which were increased in the PAH group. CONCLUSION: Intervention with BB mitigated functional PAH outcomes through improvement of the pulmonary redox state. Our results provide a basis for future research on natural antioxidant interventions as a novel treatment strategy in PAH.
Authors: Grazielle S De Oliveira; Gislaine S Pinheiro; Isabel C T Proença; Amanda Blembeel; Marcela Z Casal; Daniela Pochmann; Leonardo Tartaruga; Flavia G Martinez; Alex Sander Araújo; Viviane Elsner; Caroline Dani Journal: Heliyon Date: 2021-02-05
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Authors: Patrick Türck; Isadora Schein Salvador; Cristina Campos-Carraro; Vanessa Ortiz; Alan Bahr; Michael Andrades; Adriane Belló-Klein; Alex Sander da Rosa Araujo Journal: Eur J Nutr Date: 2021-08-10 Impact factor: 5.614
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