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Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

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CAF reduced tubular cell injury and granulocyte infiltration in an experimental model of kidney ischemia-reperfusion injury in C57BL-6 mice.(A) Hematoxylin/eosin staining of representative kidney sections from different experimental groups of C57BL-6 mice (n = 6 for each group): sham-operated (SHAM); right kidney ischemia-reperfusion injury (IRI); right kidney ischemia-reperfusion injury + Caffeic acid 1μM/ml (IRI + CAF). Original magnification was x40. Counts of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells (B) and of granulocyte infiltration (C) in the different experimental conditions. A significant increase of apoptotic tubular cells and infiltrating granulocytes was observed in IRI in comparison with sham-treated animals (#p<0.05 IRI vs. SHAM). CAF induced a significant decrease of apoptotic tubular cells and granulocyte infiltration in mice subjected to IRI (*p<0.05 IRI + CAF vs. IRI). In B and C, results are expressed as average±1SD in 30 non-consecutive fields.
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pone.0117530.g011: CAF reduced tubular cell injury and granulocyte infiltration in an experimental model of kidney ischemia-reperfusion injury in C57BL-6 mice.(A) Hematoxylin/eosin staining of representative kidney sections from different experimental groups of C57BL-6 mice (n = 6 for each group): sham-operated (SHAM); right kidney ischemia-reperfusion injury (IRI); right kidney ischemia-reperfusion injury + Caffeic acid 1μM/ml (IRI + CAF). Original magnification was x40. Counts of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells (B) and of granulocyte infiltration (C) in the different experimental conditions. A significant increase of apoptotic tubular cells and infiltrating granulocytes was observed in IRI in comparison with sham-treated animals (#p<0.05 IRI vs. SHAM). CAF induced a significant decrease of apoptotic tubular cells and granulocyte infiltration in mice subjected to IRI (*p<0.05 IRI + CAF vs. IRI). In B and C, results are expressed as average±1SD in 30 non-consecutive fields.

Mentions: In comparison to sham-operated animals, mice subjected to kidney ischemia-reperfusion injury showed histological signs of tubular injury such as formation of hyaline casts, vacuolization, diffuse necrosis and denudation of basal membrane. When mice were treated with 1μM/ml CAF, a significant reduction of tubular injury was observed (Fig. 11A and Table 1). In addition, CAF significantly reduced the number of apoptotic tubular cells (Fig. 11B) and granulocyte infiltration (Fig. 11C) within ischemic kidney.


Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

CAF reduced tubular cell injury and granulocyte infiltration in an experimental model of kidney ischemia-reperfusion injury in C57BL-6 mice.(A) Hematoxylin/eosin staining of representative kidney sections from different experimental groups of C57BL-6 mice (n = 6 for each group): sham-operated (SHAM); right kidney ischemia-reperfusion injury (IRI); right kidney ischemia-reperfusion injury + Caffeic acid 1μM/ml (IRI + CAF). Original magnification was x40. Counts of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells (B) and of granulocyte infiltration (C) in the different experimental conditions. A significant increase of apoptotic tubular cells and infiltrating granulocytes was observed in IRI in comparison with sham-treated animals (#p<0.05 IRI vs. SHAM). CAF induced a significant decrease of apoptotic tubular cells and granulocyte infiltration in mice subjected to IRI (*p<0.05 IRI + CAF vs. IRI). In B and C, results are expressed as average±1SD in 30 non-consecutive fields.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4390339&req=5

pone.0117530.g011: CAF reduced tubular cell injury and granulocyte infiltration in an experimental model of kidney ischemia-reperfusion injury in C57BL-6 mice.(A) Hematoxylin/eosin staining of representative kidney sections from different experimental groups of C57BL-6 mice (n = 6 for each group): sham-operated (SHAM); right kidney ischemia-reperfusion injury (IRI); right kidney ischemia-reperfusion injury + Caffeic acid 1μM/ml (IRI + CAF). Original magnification was x40. Counts of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells (B) and of granulocyte infiltration (C) in the different experimental conditions. A significant increase of apoptotic tubular cells and infiltrating granulocytes was observed in IRI in comparison with sham-treated animals (#p<0.05 IRI vs. SHAM). CAF induced a significant decrease of apoptotic tubular cells and granulocyte infiltration in mice subjected to IRI (*p<0.05 IRI + CAF vs. IRI). In B and C, results are expressed as average±1SD in 30 non-consecutive fields.
Mentions: In comparison to sham-operated animals, mice subjected to kidney ischemia-reperfusion injury showed histological signs of tubular injury such as formation of hyaline casts, vacuolization, diffuse necrosis and denudation of basal membrane. When mice were treated with 1μM/ml CAF, a significant reduction of tubular injury was observed (Fig. 11A and Table 1). In addition, CAF significantly reduced the number of apoptotic tubular cells (Fig. 11B) and granulocyte infiltration (Fig. 11C) within ischemic kidney.

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Show MeSH
Related in: MedlinePlus