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. 2025 Mar 26;17(7):1145.
doi: 10.3390/nu17071145.

Blueberry Extract and Resistance Training Prevent Left Ventricular Redox Dysregulation and Pathological Remodeling in Experimental Severe Pulmonary Arterial Hypertension

Luciano Bernardes Leite  1   2 , Leôncio Lopes Soares  1 , Luiz Otávio Guimarães-Ervilha  3 , Sebastião Felipe Ferreira Costa  1 , Sara Caco Dos Lúcio Generoso  1 , Mirielly Alexia Miranda Xavier  3 , Thainá Iasbik-Lima  3 , Leandro Licursi de Oliveira  3 , Ceres Mattos Della Lucia  4 , Sara Elis Bianchi  5 , Valquíria Linck Bassani  5 , Flavio Gilberto Herter  6 , Patrick Turck  7 , Alex Sander da Rosa Araujo  7 , Pedro Forte  2   8   9   10 , Emily Correna Carlo Reis  11 , Mariana Machado-Neves  3 , Antônio José Natali  1
Affiliations

Blueberry Extract and Resistance Training Prevent Left Ventricular Redox Dysregulation and Pathological Remodeling in Experimental Severe Pulmonary Arterial Hypertension

Luciano Bernardes Leite et al. Nutrients. .

Abstract

Objective: To investigate whether the regular administration of blueberry extract and low-intensity resistance exercise training (RT), either alone or in combination, during the development of monocrotaline (MCT)-induced severe pulmonary arterial hypertension (PAH) in rats protect the left ventricle (LV) from redox dysregulation and pathological remodeling.

Methods: Groups of seven male Wistar rats were formed for the experiment: sedentary control; sedentary hypertensive; sedentary hypertensive blueberry; exercise hypertensive; and exercise hypertensive blueberry. PAH was experimentally induced through a single intraperitoneal administration of MCT at a dose of 60 mg/kg. One day after injection, the blueberry groups started receiving a daily dose of blueberry extract (100 mg/kg) by gavage, while the exercise groups initiated a three-week program of RT (ladder climbing; 15 climbs carrying 60% of maximum load; one session/day; 5 times/week). Echocardiographic evaluations were conducted 23 days after injection, and the rats were euthanized the next day to harvest LV tissue.

Results: Separately, blueberry extract and RT mitigated augments in pulmonary artery resistance, LV tissue redox dysregulation (i.e., increased PC levels) and detrimental remodeling (i.e., reduced inflammation), and reductions in ejection fraction (EF) and fractional shortening (FS) caused by PAH. The combination of treatments prevented reductions in EF and FS, along with the development of a D-shaped LV.

Conclusions: blueberry extract and moderate-intensity resistance training administered during the development of MCT-induced severe PAH in rats prevented LV redox dysregulation and pathological remodeling, thereby preserving its function.

Keywords: adverse remodeling; blueberry extract; ejection fraction; exercise training; left ventricle; pulmonary artery resistance; redox state.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of the study design with its respective analyses.
Figure 2
Figure 2
Effects of blueberry extract and resistance training on left ventricular function. (A) Representative echocardiograph images. (B) D-shaped left ventricle. (C) Ejection fraction. (D) Fractional shortening. The data are expressed as means ± SEM of seven rats per group. SC—sedentary control; SH—sedentary hypertensive; SHB—sedentary hypertensive blueberry; EH—hypertensive exercise; EHB—exercise hypertensive blueberry. * p < 0.05 vs. SC; # p < 0.05 vs. SH. Panel (A) (Fisher’s exact test). Panel (B,C) (one-way ANOVA followed by Tukey’s post hoc test).
Figure 3
Figure 3
Effects of blueberry extract and resistance training on cardiac morphometric parameters. (A) Heart weight (HW). (B) Left ventricular weight (LVW). (C) Heart weight/tibial length (HW/TL). (D) Left ventricular weight/tibial length (LVW/TL). The data are expressed as means ± SEM of seven rats per group. SC—sedentary control; SH—sedentary hypertensive; SHB—sedentary hypertensive blueberry; EH—hypertensive exercise; EHB—exercise hypertensive blueberry. * p < 0.05 vs. SC; # p < 0.05 vs. SH. One-way ANOVA followed by Tukey’s post hoc test.
Figure 4
Figure 4
(A–O) Representative photomicrographs of left ventricle tissue stained with hematoxylin and eosin (scale bar: 50 μm). SC—sedentary control; SH—sedentary hypertensive; SHB—sedentary hypertensive treated with blueberry extract; EH—hypertensive treated with resistance training; EHB—hypertensive treated with combined blueberry extract and resistance training. Black arrows: cardiomyocytes; arrowheads: extracellular matrix; asterisks: inflammatory foci; dotted regions: areas of cell death. Data are expressed as means ± SEM of seven rats per group.
Figure 5
Figure 5
Effects of blueberry extract and resistance training on left ventricular collagen deposition. (A) Representative photomicrographs of LV tissue stained with Sirius red. (B) Percentage of type I collagen. (C) Percentage of type III collagen. (D) Percentage of total collagen. The data are expressed as means ± SEM of seven rats per group. SC—sedentary control; SH—sedentary hypertensive; SHB—sedentary hypertensive blueberry; EH—hypertensive exercise; EHB—exercise hypertensive blueberry. Yellow arrows: Type I collagen; blue arrows: Type III collagen. One-way ANOVA followed by Tukey’s post hoc test. * p < 0.05 vs. SC.
Figure 6
Figure 6
Effects of blueberry extract and resistance training on left ventricular oxidative stress biomarkers. (A) CAT (catalase), (B) SOD (superoxide dismutase), (C) GST (glutathione S-transferase), (D) MDA (malondialdehyde), (E) NO (nitric oxide), (F) PC (protein carbonyl). The data are expressed as means ± SEM for five or seven rats per group. SC—sedentary control; SH—sedentary hypertensive; SHB—sedentary hypertensive blueberry; EH—hypertensive exercise; EHB—exercise hypertensive blueberry. One-way ANOVA followed by Tukey’s post hoc test. * p ˂ 0.05 vs. SC; # p ˂ 0.05 vs. SH.
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