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 language | English |
|---|---|
| Pages (from-to) | 1465-1479 |
| Number of pages | 15 |
| Journal | Journal of Hypertension |
| Volume | 33 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2015 |
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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 journal › Article
}
TY - JOUR
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.
AB - 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.
KW - AMPK/PGC1α/SIRT1/PPARα/UCP2
KW - Brassica oleracea
KW - High-salt diet
KW - Hypertension
KW - Renal damage
KW - Stroke-prone spontaneously hypertensive rat
UR - http://www.scopus.com/inward/record.url?scp=84938865951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938865951&partnerID=8YFLogxK
U2 - 10.1097/HJH.0000000000000562
DO - 10.1097/HJH.0000000000000562
M3 - Article
VL - 33
SP - 1465
EP - 1479
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 7
ER -