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

Q: What are the key findings of this study?

Blueberry extract and resistance training mitigated pulmonary artery resistance (TA/TE 0.44 vs 0.22 in untreated rats) and prevented LV redox dysregulation and EF/FS reductions in rat PAH.

Q: What is the clinical evidence from this study?

Population: Monocrotaline-induced severe pulmonary arterial hypertension (n=35). Intervention: Blueberry extract and resistance exercise training, alone or in combination vs. Sedentary untreated hypertensive rats (injected with monocrotaline 60 mg/kg) and sedentary healthy controls (injected with saline). Primary outcome: Pulmonary artery flow dynamics (acceleration time to ejection time ratio [TA/TE]), left ventricular function (EF, FS), redox dysregulation, and pathological remodeling at 23-24 days (p=<0.05).

Q: What does this research mean for the field?

Blueberry extract and resistance exercise training prevent left ventricular redox dysregulation, pathological remodeling, and systolic dysfunction during the progression of monocrotaline-induced severe pulmonary arterial hypertension in rats. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To examine whether daily blueberry extract and low-intensity resistance exercise training, administered individually or in combination, protect the left ventricle from redox dysregulation and adverse remodeling in rats with monocrotaline-induced severe pulmonary arterial hypertension.

Luciano Bernardes Leite; Leôncio Lopes Soares; Luiz Otávio Guimarães‐Ervilha; Sebastião Felipe Ferreira Costa; Sara Caco dos Lúcio Generoso; Thainá Iasbik‐Lima; Leandro Licursi de Oliveira; Ceres Mattos Della Lúcia; Sara Elis Bianchi; Valquíria Linck Bassani; Flávio Gilberto Herter; Patrick Türck; Alex Sander da Rosa Araújo; Pedro Forte; Emily Correna Carlo Reis; Mariana Machado‐Neves; Antônio José Natali

doi:10.3390/nu17071145

March 26, 2025NutrientsOpen Access

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

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Key result

Blueberry extract plus resistance training doubles pulmonary flow ratio and preserves LV function in rat PAH.

P<0.05
n=35

Figures

Why the study?

To investigate whether blueberry extract and low-intensity resistance exercise training, alone or combined, protect the left ventricle from redox dysregulation and pathological remodeling during MCT-induced severe PAH in rats.

Does regular administration of blueberry extract and resistance exercise training, alone or in combination, prevent left ventricular redox dysregulation, pathological remodeling, and functional decline in rats with monocrotaline-induced severe pulmonary arterial hypertension?

Key Points

To examine whether daily blueberry extract and low-intensity resistance exercise training, administered individually or in combination, protect the left ventricle from redox dysregulation and adverse remodeling in rats with monocrotaline-induced severe pulmonary arterial hypertension.
Seven male Wistar rats per group were assigned to sedentary control, sedentary hypertensive, sedentary hypertensive blueberry, exercise hypertensive, or exercise hypertensive blueberry groups.
Pulmonary arterial hypertension was induced via a single intraperitoneal dose of monocrotaline (60 mg/kg), followed by daily blueberry extract (100 mg/kg) and/or ladder-climbing resistance training (15 climbs at 60% maximum load, 5 times/week for 3 weeks).
Echocardiographic measurements were conducted 23 days post-injection before euthanizing the animals the next day to evaluate left ventricular histology and oxidative stress markers.
Untreated hypertensive rats had lower pulmonary artery flow TA/TE values (0.22 ± 0.01) than controls (0.61 ± 0.02), whereas values improved in the sedentary blueberry (0.39 ± 0.01), exercise (0.45 ± 0.02), and combined groups (0.44 ± 0.02).
Severe hypertension reduced ejection fraction and fractional shortening, triggered interventricular septal flattening, and raised protein carbonyl levels; individual interventions alleviated functional declines, while combined treatment fully preserved function and prevented septal flattening.
Untreated hypertensive rats exhibited elevated type I and total collagen percentages (p < 0.05 vs controls), though collagen reductions across the treatment groups did not achieve statistical significance.

Structured PICO

Does regular administration of blueberry extract and resistance exercise training, alone or in combination, prevent left ventricular redox dysregulation, pathological remodeling, and functional decline in rats with monocrotaline-induced severe pulmonary arterial hypertension?

P

Population

35 male Wistar rats (~200 g) in an experimental model of monocrotaline-induced severe pulmonary arterial hypertension, evaluated over 24 days.

I

Intervention

Daily oral gavage of blueberry (Vaccinium myrtillus) extract at 100 mg/kg/day (containing 38.89 mg GAE/g phenolics, 219.21 µg/mL cyanidin, and 128.68 µg/mL malvidin) and/or low-to-moderate intensity resistance exercise training (vertical ladder climbing, 15 climbs/session carrying 60% of maximum load, 60 s rest between climbs, 1 session/day, 5 days/week) initiated 1 day after monocrotaline injection until day 23-24.

C

Comparator

Sedentary hypertensive rats (monocrotaline 60 mg/kg i.p. without blueberry or exercise) and sedentary control rats (equivalent volume of 140 mM NaCl saline solution i.p.).

O

Outcome

Left ventricular function (ejection fraction [EF], fractional shortening [FS], D-shaped interventricular septal flattening) and pulmonary artery hemodynamic resistance (acceleration time to ejection time [TA/TE] ratio) evaluated by echocardiography at 23 days, plus LV tissue redox dysregulation (SOD, CAT, GST, NO, MDA, protein carbonyls) and pathological remodeling (heart weight, inflammation, collagen deposition) at day 24.surrogate

Main Result

Absolute Event Rate: 0.44% vs 0.22%

p-value: p=<0.05

In a rat model of severe pulmonary arterial hypertension, combining oral blueberry extract with resistance training synergistically prevented left ventricular oxidative stress, septal flattening, and systolic dysfunction.

Limitations

Cannot completely rule out the direct effects of monocrotaline on the left ventricle.
Chemical composition of blueberry extracts can vary depending on growing, harvesting, and processing factors.
Protease inhibitors were not used during sample processing, which may have led to partial protein degradation and influenced enzymatic activity accuracy.
No serial echocardiographic assessments were performed to monitor PAH progression, and cardiac efficiency could not be calculated due to limited access to advanced imaging.
Protease inhibitors were not used during sample processing, which may have led to partial protein degradation and influenced enzymatic activity values.
Serial echocardiographic assessments were not performed to monitor PAH progression, and cardiac efficiency could not be calculated due to limited access to advanced imaging techniques.

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Implication

May support adjunctive testing in experimental PAH; hypothesis-generating and should not change clinical practice.

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.

Discussion

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Cite This Study

Leite et al. (2025) studied Monocrotaline-induced severe pulmonary arterial hypertension (n=35). Blueberry extract and resistance exercise training, alone or in combination vs. Sedentary untreated hypertensive rats (injected with monocrotaline 60 mg/kg) and sedentary healthy controls (injected with saline) was evaluated on Pulmonary artery flow dynamics (acceleration time to ejection time ratio [TA/TE]), left ventricular function (EF, FS), redox dysregulation, and pathological remodeling at 23-24 days (p=<0.05). Blueberry extract and resistance training mitigated pulmonary artery resistance (TA/TE 0.44 vs 0.22 in untreated rats) and prevented LV redox dysregulation and EF/FS reductions in rat PAH.

synapsesocial.com/papers/6a7ca7f5d8712010ad4c752c https://doi.org/10.3390/nu17071145

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

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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