Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP

Role of AMPK/PPARa/UCP2 axis

Speranza Rubattu, Sara Di Castro, Maria Cotugno, Franca Bianchi, Roberto Mattioli, Simona Baima, Rosita Stanzione, Michele Madonna, Cristina Bozzao, Simona Marchitti, Paolo Gelosa, Luigi Sironi, Alice Pignieri, Mariateresa Maldini, Anna Maria Giusti, Mirella Nardini, Giorgio Morelli, Paolo Costantino, Massimo Volpe

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objectives: Renal damage precedes occurrence of stroke in high-sodium/low-potassium-fed stroke-prone spontaneously hypertensive rat (SHRSP). We previously reported a marked suppression of uncoupling protein-2 (UCP2) upon high-salt Japanese-style diet in SHRSP kidneys. Vegetable compounds are known to exert protective effects in cardiovascular diseases. We aimed at evaluating the impact of Brassica oleracea sprouts juice toward renal damage in Japanese diet-fed SHRSP and exploring the role of 5'-adenosine monophosphateactivated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1)/peroxisome proliferatoractivated receptor-γ coactivator-1α (PGC1α)/peroxisome proliferator-activated receptor-α (PPARα)/UCP2 axis. Methods: SHRSP received Japanese diet for 4 weeks. A group of SHRSP received Japanese diet and B. Oleracea. A third group received Japanese diet, B. Oleracea, and PPARα inhibitor (GW6471). A group of SHRSP fed with regular diet served as control. Results: Japanese diet induced marked increases of oxidative stress, inflammation, and proteinuria, along with glomerular and tubular damage, as compared with regular diet. A significant suppression of AMPK/UCP2 pathway was observed. Despite Japanese diet feeding, concomitant administration of B. Oleracea prevented oxidative stress accumulation, inflammation, renal damage, and proteinuria. All components of the UCP2 regulatory pathway were significantly increased by B. Oleracea. Superoxide dismutase 2 and phosphoendothelial nitric oxide synthase were also stimulated. Addition of PPARa inhibitor to B. Oleracea and Japanese diet significantly reduced the B. Oleracea beneficial effects. SBP levels were comparable among the different groups of rats. In vitro, UCP2 inhibition by genipin offset the antioxidant effect of B. Oleracea in renal mesangial and proximal tubular cells. Conclusion: B. Oleracea administration prevented renal damage in salt-loaded SHRSP, independently from SBP, with parallel stimulation of AMPK/SIRT1/PGC1α/PPARα/UCP2 axis. Stimulation of the latter mechanism may provide relevant renal protective effect and play a therapeutic role in target organ damage progression in hypertension.

Original languageEnglish
Pages (from-to)1465-1479
Number of pages15
JournalJournal of Hypertension
Volume33
Issue number7
DOIs
Publication statusPublished - 2015

Fingerprint

Brassica
Adenosine
Protein Kinases
Salts
Diet
Kidney
Peroxisome Proliferator-Activated Receptors
Sirtuin 1
Proteinuria
Oxidative Stress
Stroke
Uncoupling Protein 2
Inflammation
Peroxisomes
Inbred SHR Rats
Nitric Oxide Synthase
Vegetables
NAD
Potassium
Cardiovascular Diseases

Keywords

  • AMPK/PGC1α/SIRT1/PPARα/UCP2
  • Brassica oleracea
  • High-salt diet
  • Hypertension
  • Renal damage
  • Stroke-prone spontaneously hypertensive rat

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP : Role of AMPK/PPARa/UCP2 axis. / Rubattu, Speranza; Di Castro, Sara; Cotugno, Maria; Bianchi, Franca; Mattioli, Roberto; Baima, Simona; Stanzione, Rosita; Madonna, Michele; Bozzao, Cristina; Marchitti, Simona; Gelosa, Paolo; Sironi, Luigi; Pignieri, Alice; Maldini, Mariateresa; Giusti, Anna Maria; Nardini, Mirella; Morelli, Giorgio; Costantino, Paolo; Volpe, Massimo.

In: Journal of Hypertension, Vol. 33, No. 7, 2015, p. 1465-1479.

Research output: Contribution to journalArticle

Rubattu, S, Di Castro, S, Cotugno, M, Bianchi, F, Mattioli, R, Baima, S, Stanzione, R, Madonna, M, Bozzao, C, Marchitti, S, Gelosa, P, Sironi, L, Pignieri, A, Maldini, M, Giusti, AM, Nardini, M, Morelli, G, Costantino, P & Volpe, M 2015, 'Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP: Role of AMPK/PPARa/UCP2 axis', Journal of Hypertension, vol. 33, no. 7, pp. 1465-1479. https://doi.org/10.1097/HJH.0000000000000562
Rubattu, Speranza ; Di Castro, Sara ; Cotugno, Maria ; Bianchi, Franca ; Mattioli, Roberto ; Baima, Simona ; Stanzione, Rosita ; Madonna, Michele ; Bozzao, Cristina ; Marchitti, Simona ; Gelosa, Paolo ; Sironi, Luigi ; Pignieri, Alice ; Maldini, Mariateresa ; Giusti, Anna Maria ; Nardini, Mirella ; Morelli, Giorgio ; Costantino, Paolo ; Volpe, Massimo. / Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP : Role of AMPK/PPARa/UCP2 axis. In: Journal of Hypertension. 2015 ; Vol. 33, No. 7. pp. 1465-1479.
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abstract = "Objectives: Renal damage precedes occurrence of stroke in high-sodium/low-potassium-fed stroke-prone spontaneously hypertensive rat (SHRSP). We previously reported a marked suppression of uncoupling protein-2 (UCP2) upon high-salt Japanese-style diet in SHRSP kidneys. Vegetable compounds are known to exert protective effects in cardiovascular diseases. We aimed at evaluating the impact of Brassica oleracea sprouts juice toward renal damage in Japanese diet-fed SHRSP and exploring the role of 5'-adenosine monophosphateactivated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1)/peroxisome proliferatoractivated receptor-γ coactivator-1α (PGC1α)/peroxisome proliferator-activated receptor-α (PPARα)/UCP2 axis. Methods: SHRSP received Japanese diet for 4 weeks. A group of SHRSP received Japanese diet and B. Oleracea. A third group received Japanese diet, B. Oleracea, and PPARα inhibitor (GW6471). A group of SHRSP fed with regular diet served as control. Results: Japanese diet induced marked increases of oxidative stress, inflammation, and proteinuria, along with glomerular and tubular damage, as compared with regular diet. A significant suppression of AMPK/UCP2 pathway was observed. Despite Japanese diet feeding, concomitant administration of B. Oleracea prevented oxidative stress accumulation, inflammation, renal damage, and proteinuria. All components of the UCP2 regulatory pathway were significantly increased by B. Oleracea. Superoxide dismutase 2 and phosphoendothelial nitric oxide synthase were also stimulated. Addition of PPARa inhibitor to B. Oleracea and Japanese diet significantly reduced the B. Oleracea beneficial effects. SBP levels were comparable among the different groups of rats. In vitro, UCP2 inhibition by genipin offset the antioxidant effect of B. Oleracea in renal mesangial and proximal tubular cells. Conclusion: B. Oleracea administration prevented renal damage in salt-loaded SHRSP, independently from SBP, with parallel stimulation of AMPK/SIRT1/PGC1α/PPARα/UCP2 axis. Stimulation of the latter mechanism may provide relevant renal protective effect and play a therapeutic role in target organ damage progression in hypertension.",
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T1 - Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP

T2 - Role of AMPK/PPARa/UCP2 axis

AU - Rubattu, Speranza

AU - Di Castro, Sara

AU - Cotugno, Maria

AU - Bianchi, Franca

AU - Mattioli, Roberto

AU - Baima, Simona

AU - Stanzione, Rosita

AU - Madonna, Michele

AU - Bozzao, Cristina

AU - Marchitti, Simona

AU - Gelosa, Paolo

AU - Sironi, Luigi

AU - Pignieri, Alice

AU - Maldini, Mariateresa

AU - Giusti, Anna Maria

AU - Nardini, Mirella

AU - Morelli, Giorgio

AU - Costantino, Paolo

AU - Volpe, Massimo

PY - 2015

Y1 - 2015

N2 - Objectives: Renal damage precedes occurrence of stroke in high-sodium/low-potassium-fed stroke-prone spontaneously hypertensive rat (SHRSP). We previously reported a marked suppression of uncoupling protein-2 (UCP2) upon high-salt Japanese-style diet in SHRSP kidneys. Vegetable compounds are known to exert protective effects in cardiovascular diseases. We aimed at evaluating the impact of Brassica oleracea sprouts juice toward renal damage in Japanese diet-fed SHRSP and exploring the role of 5'-adenosine monophosphateactivated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1)/peroxisome proliferatoractivated receptor-γ coactivator-1α (PGC1α)/peroxisome proliferator-activated receptor-α (PPARα)/UCP2 axis. Methods: SHRSP received Japanese diet for 4 weeks. A group of SHRSP received Japanese diet and B. Oleracea. A third group received Japanese diet, B. Oleracea, and PPARα inhibitor (GW6471). A group of SHRSP fed with regular diet served as control. Results: Japanese diet induced marked increases of oxidative stress, inflammation, and proteinuria, along with glomerular and tubular damage, as compared with regular diet. A significant suppression of AMPK/UCP2 pathway was observed. Despite Japanese diet feeding, concomitant administration of B. Oleracea prevented oxidative stress accumulation, inflammation, renal damage, and proteinuria. All components of the UCP2 regulatory pathway were significantly increased by B. Oleracea. Superoxide dismutase 2 and phosphoendothelial nitric oxide synthase were also stimulated. Addition of PPARa inhibitor to B. Oleracea and Japanese diet significantly reduced the B. Oleracea beneficial effects. SBP levels were comparable among the different groups of rats. In vitro, UCP2 inhibition by genipin offset the antioxidant effect of B. Oleracea in renal mesangial and proximal tubular cells. Conclusion: B. Oleracea administration prevented renal damage in salt-loaded SHRSP, independently from SBP, with parallel stimulation of AMPK/SIRT1/PGC1α/PPARα/UCP2 axis. Stimulation of the latter mechanism may provide relevant renal protective effect and play a therapeutic role in target organ damage progression in hypertension.

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KW - Brassica oleracea

KW - High-salt diet

KW - Hypertension

KW - Renal damage

KW - Stroke-prone spontaneously hypertensive rat

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