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Article ; Online: Subacute administration of cilostazol modulates PLC-γ/PKC-α/p38/NF-kB pathway and plays vascular protective effects through eNOS activation in early stages of atherosclerosis development.

Brazão, Stephani Correia / Lima, Gabriel Ferreira / Autran, Lis Jappour / Mendes, Ana Beatriz Araújo / Dos Santos, Beatriz Alexandre / Magliano, Dangelo Carlo / de Brito, Fernanda Carla Ferreira / Motta, Nadia Alice Vieira

Life sciences

2023 Volume 332, Page(s) 122082

Abstract: Aims: Hypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 ... ...

Abstract	Aims: Hypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically prescribed for intermittent claudication treatment. Due to its pleiotropic properties, such as lipid lowering, anti-inflammatory, and antioxidant effects, the therapeutic repurposing of cilostazol has become a strategic approach for atherosclerosis treatment. This study aimed to investigate the effects of subacute administration of cilostazol on the aortas of hypercholesterolemic rats, focusing on the signaling pathways involved in these actions. Main methods: A murine model of hypercholesterolemia was employed to mimic the early stages of atherosclerosis development. Vascular reactivity assays were performed on thoracic aorta rings to assess the vascular response, as well as the non-invasive blood pressure was evaluated by plethysmography method. Pro-inflammatory markers and malondialdehyde (MDA) levels were measured to investigate the anti-inflammatory and antioxidant effects of cilostazol. Western Blot analysis was performed in aortas homogenates to evaluate the role of cilostazol on PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB and PKA/eNOS/PKG pathways. Key findings: The hypercholesterolemic diet induced the production of pro-inflammatory mediators such as TNF-α, TXB Significance: Cilostazol suppressed hypercholesterolemia-induced vascular dysfunction and inflammation. Our data suggest the potential repurposing of cilostazol as a pharmacological treatment for atherosclerosis.
Language	English
Publishing date	2023-09-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.122082
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Article ; Online: Could cilostazol be beneficial in COVID-19 treatment? Thinking about phosphodiesterase-3 as a therapeutic target.

Motta, Nadia Alice Vieira / Autran, Lis Jappour / Brazão, Stephani Correia / Lopes, Rosane de Oliveira / Scaramello, Christianne Brêtas Vieira / Lima, Gabriel Ferreira / Brito, Fernanda Carla Ferreira de

International immunopharmacology

2020 Volume 92, Page(s) 107336

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that has emerged and rapidly spread across the world. The COVID-19 severity is associated to viral pneumonia with additional extrapulmonary ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that has emerged and rapidly spread across the world. The COVID-19 severity is associated to viral pneumonia with additional extrapulmonary complications. Hyperinflammation, dysfunctional immune response and hypercoagulability state are associated to poor prognosis. Therefore, the repositioning of multi-target drugs to control the hyperinflammation represents an important challenge for the scientific community. Cilostazol, a selective phosphodiesterase type-3 inhibitor (PDE-3), is an antiplatelet and vasodilator drug, that presents a range of pleiotropic effects, such as antiapoptotic, anti-inflammatory, antioxidant, and cardioprotective activities. Cilostazol also can inhibit the adenosine uptake, which enhances intracellular cAMP levels. In the lungs, elevated cAMP promotes anti-fibrotic, vasodilator, antiproliferative effects, as well as mitigating inflammatory events. Interestingly, a recent study evaluated antiplatelet FDA-approved drugs through molecular docking-based virtual screening on viral target proteins. This study revealed that cilostazol is a promising drug against COVID-19 by inhibiting both main protease (M
MeSH term(s)	Cilostazol/therapeutic use ; Humans ; Phosphodiesterase 3 Inhibitors/therapeutic use ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	Phosphodiesterase 3 Inhibitors ; Cilostazol (N7Z035406B)
Language	English
Publishing date	2020-12-28
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2020.107336
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Article ; Online: Cilostazol attenuates cardiac oxidative stress and inflammation in hypercholesterolemic rats.

de Oliveira Lopes, Rosane / Lima, Gabriel Ferreira / Mendes, Ana Beatriz Araújo / Autran, Lis Jappour / de Assis Pereira, Nikolas Cunha / Brazão, Stephani Correia / Alexandre-Santos, Beatriz / Frantz, Eliete Dalla Corte / Scaramello, Christianne Brêtas Vieira / Brito, Fernanda Carla Ferreira / Motta, Nadia Alice Vieira

Naunyn-Schmiedeberg's archives of pharmacology

2022 Volume 395, Issue 7, Page(s) 789–801

Abstract: Atherosclerosis is a multifactorial chronic disease associated with pro-inflammatory and pro-oxidative cardiovascular states. Cilostazol, a selective phosphodiesterase 3 inhibitor (PDE3), is clinically used in the treatment of intermittent claudication ... ...

Abstract	Atherosclerosis is a multifactorial chronic disease associated with pro-inflammatory and pro-oxidative cardiovascular states. Cilostazol, a selective phosphodiesterase 3 inhibitor (PDE3), is clinically used in the treatment of intermittent claudication and secondary prevention of cerebral infarction. The aim of this study was to evaluate the cardioprotective effects of cilostazol and the molecular mechanisms involved in hypercholesterolemic rats. Male Wistar rats were divided into four groups: control group (C) and control + cilostazol group (C+CILO), that were fed a standard chow diet, and hypercholesterolemic diet group (HCD) and HCD + cilostazol (HCD+CILO) that were fed a hypercholesterolemic diet. Cilostazol treatment started after 30 days for C+CILO and HCD+CILO groups. Animals were administered cilostazol once a day for 15 days. Subsequently, serum and left ventricles were extracted for evaluation of lipid profile, inflammatory, and oxidative biomarkers. The HCD group displayed increased serum lipid levels, inflammatory cytokines production, and cardiac NF-kB protein expression and decreased cardiac Nrf2-mediated antioxidant activity. Conversely, the cilostazol treatment improved all these cardiac deleterious effects, inhibiting NF-kB activation and subsequently decreasing inflammatory mediators, reestablishing the antioxidant properties through Nrf2-mediated pathway, including increased SOD, GPx, and catalase expression. Taken together, our results indicated that cilostazol protects hypercholesterolemia-induced cardiac damage by molecular mechanisms targeting the crosstalk between Nrf2 induction and NF-kB inhibition in the heart.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Cilostazol/pharmacology ; Inflammation/drug therapy ; Lipids ; Male ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Oxidative Stress ; Phosphodiesterase 3 Inhibitors/pharmacology ; Phosphodiesterase 3 Inhibitors/therapeutic use ; Rats ; Rats, Wistar
Chemical Substances	Antioxidants ; Lipids ; NF-E2-Related Factor 2 ; NF-kappa B ; Phosphodiesterase 3 Inhibitors ; Cilostazol (N7Z035406B)
Language	English
Publishing date	2022-04-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-022-02233-3
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Article ; Online: Subacute administration of cilostazol modulates PLC-γ/PKC-α/p38/NF-kB pathway and plays vascular protective effects through eNOS activation in early stages of atherosclerosis development

Brazão, Stephani Correia / Lima, Gabriel Ferreira / Autran, Lis Jappour / Mendes, Ana Beatriz Araújo / dos Santos, Beatriz Alexandre / Magliano, Dangelo Carlo / de Brito, Fernanda Carla Ferreira / Motta, Nadia Alice Vieira

Life Sciences. 2023 Sept. 16, p.122082-

2023 , Page(s) 122082–

Abstract: Hypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically ... ...

Abstract	Hypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically prescribed for intermittent claudication treatment. Due to its pleiotropic properties, such as lipid lowering, anti-inflammatory, and antioxidant effects, the therapeutic repurposing of cilostazol has become a strategic approach for atherosclerosis treatment. This study aimed to investigate the effects of subacute administration of cilostazol on the aortas of hypercholesterolemic rats, focusing on the signaling pathways involved in these actions. A murine model of hypercholesterolemia was employed to mimic the early stages of atherosclerosis development. Vascular reactivity assays were performed on thoracic aorta rings to assess the vascular response, as well as the non-invasive blood pressure was evaluated by plethysmography method. Pro-inflammatory markers and malondialdehyde (MDA) levels were measured to investigate the anti-inflammatory and antioxidant effects of cilostazol. Western Blot analysis was performed in aortas homogenates to evaluate the role of cilostazol on PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB and PKA/eNOS/PKG pathways. The hypercholesterolemic diet induced the production of pro-inflammatory mediators such as TNF-α, TXB₂, VCAM, and worsened vascular function, marked by increased contractile response, decreased maximum relaxation, and elevated systolic and diastolic blood pressure. Cilostazol seems to counteract the deleterious effects promoted by hypercholesterolemic diet, showing important anti-inflammatory and vasculoprotective properties possibly through the inhibition of the PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB pathway and activation of the PKA/eNOS/PKG pathway. Cilostazol suppressed hypercholesterolemia-induced vascular dysfunction and inflammation. Our data suggest the potential repurposing of cilostazol as a pharmacological treatment for atherosclerosis.
Keywords	Western blotting ; animal models ; antioxidants ; aorta ; atherosclerosis ; diastolic blood pressure ; diet ; hypercholesterolemia ; inflammation ; lipids ; malondialdehyde ; medicine ; plethysmography ; risk factors ; therapeutics ; NO ; eNOS ; ROS ; SMCs ; cGMP ; PKG ; cAMP ; PDEi ; TNF ; NF-κB ; PLCγ ; IP3 ; DAG ; PKC-α ; ICAM-1 ; VCAM-1 ; MAPK ; HCD ; TBARS ; SBP ; DBP ; Ach ; iNOS ; LDL ; VLDL ; HDL ; SOD ; GPx ; Nrf2 ; HO-1 ; NQO-1 ; AMPK ; SHR ; PKA ; PKC ; Vascular reactivity ; Cilostazol ; Endothelial dysfunction
Language	English
Dates of publication	2023-0916
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.122082
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Article: Evaluation of the effects produced by subacute tributyltin administration on vascular reactivity of male wistar rats

Mendes, Ana Beatriz Araújo / Motta, Nadia Alice Vieira / Lima, Gabriel Ferreira / Autran, Lis Jappour / Brazão, Stephani Correia / Magliano, D’Angelo Carlo / Sepúlveda-Fragoso, Vinícius / Scaramello, Christianne Brêtas Vieira / Graceli, Jones Bernardes / Miranda-Alves, Leandro / Brito, Fernanda Carla Ferreira

Toxicology. 2022 Jan. 15, v. 465

2022

Abstract: Tributyltin chloride (TBT) is an organotin compound widely used in several high biocides for agroindustrial applications, such as fungicides, and marine antifouling paints leading to endocrine disrupting actions, such as imposex development in mollusks. ... ...

Abstract	Tributyltin chloride (TBT) is an organotin compound widely used in several high biocides for agroindustrial applications, such as fungicides, and marine antifouling paints leading to endocrine disrupting actions, such as imposex development in mollusks. In female rats, TBT has been shown to promote ovarian dysfunction, reduction of estrogen protective effect in the vascular morphophysiology, at least in part by oxidative stress consequences. Estrogen causes coronary endothelium-dependent and independent vasodilation. However, the TBT effects on cardiovascular system of male rats are not fully understood. The aim of this study was to evaluate the effects of subacute TBT exposure in aorta vascular reactivity from male wistar rats. Rats were randomly divided into three groups: control (C), TBT 500 ng/kg/day and TBT 1000 ng/kg/day. TBT was administered daily for 30 days by oral gavage. We found that TBT exposure enhanced testosterone serum levels and it was also observed obesogenic properties. TBT exposure evoked an increase in endothelium-dependent and independent phenylephrine-induced contraction, associated to an inhibition in eNOS activity. On the other hand, it was observed an enhancement of iNOS and NF-kB protein expression. We also observed an increase in oxidative stress parameters, such as superoxide dismutase (SOD) and catalase expression, and also an increase in malondialdehyde production. Finally, TBT exposure produced aortic intima-media thickness. Taken together, these data suggest a potential cardiovascular toxicological effect after subacute TBT exposure in male rats.
Keywords	aorta ; biocides ; blood serum ; catalase ; estrogens ; females ; males ; malondialdehyde ; oxidative stress ; protective effect ; protein synthesis ; sex differentiation disorders ; superoxide dismutase ; testosterone ; toxicology ; transcription factor NF-kappa B ; tri-n-butyltin hydride ; tributyltin ; vasodilation
Language	English
Dates of publication	2022-0115
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2021.153067
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Article ; Online: Cilostazol exerts antiplatelet and anti-inflammatory effects through AMPK activation and NF-kB inhibition on hypercholesterolemic rats.

da Motta, Nadia Alice Vieira / de Brito, Fernanda Carla Ferreira

Fundamental & clinical pharmacology

2016 Volume 30, Issue 4, Page(s) 327–337

Abstract: This work presents a model of rats fed a high-cholesterol diet, receiving a long-term oral administration of cilostazol, a PDE3-inhibitor. The aim of this study was to evaluate the molecular mechanisms by which cilostazol interferes with platelets ... ...

Abstract	This work presents a model of rats fed a high-cholesterol diet, receiving a long-term oral administration of cilostazol, a PDE3-inhibitor. The aim of this study was to evaluate the molecular mechanisms by which cilostazol interferes with platelets signaling pathways to avoid atherosclerosis early development. Male Wistar rats were divided into 3 groups: Control group received standard rat chow (C), hypercholesterolemic group (HCD), and HCD+CIL (cilostazol group) received hypercholesterolemic diet for 45 days. HCD+CIL group received cilostazol (30 mg/kg/p.o.) once daily in the last 15 days. Platelet aggregation, lipid profile, lipid peroxidation, and cytokine serum levels were assessed. Expression of P-selectin, CD40L, PKC-α, IkB-α, and iNOS and activation of AMPK, NF-κB, and eNOS in the platelets were assessed using Western blot analysis. Cilostazol reduced the levels of total cholesterol (361.0 ± 12.8 vs. 111.5 ± 1.6 mg/dL), triglycerides (186.9 ± 17.7 vs. 55.4 ±3.1 mg/dL), cLDL (330.9 ± 9.7 vs. 61.5 ± 3.5 mg/dL), cVLDL (45.0 ± 4.6 vs. 11.1 ± 0.6 mg/dL), and malondialdehyde (9.4 ± 0.5 vs. 3.2 ± 0.3 nmol/mL) compared to the HCD group. Cilostazol presented antiplatelet properties and decreased inflammatory markers levels. These effects seem to be related to AMPK activation, NF-kB inhibition, and eNOS activation.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Enzyme Activation/physiology ; Hypercholesterolemia/drug therapy ; Hypercholesterolemia/metabolism ; Male ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Rats ; Rats, Wistar ; Tetrazoles/pharmacology ; Tetrazoles/therapeutic use ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents ; NF-kappa B ; Platelet Aggregation Inhibitors ; Tetrazoles ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; cilostazol (N7Z035406B)
Language	English
Publishing date	2016-08
Publishing country	England
Document type	Journal Article
ZDB-ID	639134-5
ISSN	1472-8206 ; 0767-3981
ISSN (online)	1472-8206
ISSN	0767-3981
DOI	10.1111/fcp.12195
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Article ; Online: Evaluation of the effects produced by subacute tributyltin administration on vascular reactivity of male wistar rats.

Mendes, Ana Beatriz Araújo / Motta, Nadia Alice Vieira / Lima, Gabriel Ferreira / Autran, Lis Jappour / Brazão, Stephani Correia / Magliano, D'Angelo Carlo / Sepúlveda-Fragoso, Vinícius / Scaramello, Christianne Brêtas Vieira / Graceli, Jones Bernardes / Miranda-Alves, Leandro / Brito, Fernanda Carla Ferreira

Toxicology

2021 Volume 465, Page(s) 153067

Abstract	Tributyltin chloride (TBT) is an organotin compound widely used in several high biocides for agroindustrial applications, such as fungicides, and marine antifouling paints leading to endocrine disrupting actions, such as imposex development in mollusks. In female rats, TBT has been shown to promote ovarian dysfunction, reduction of estrogen protective effect in the vascular morphophysiology, at least in part by oxidative stress consequences. Estrogen causes coronary endothelium-dependent and independent vasodilation. However, the TBT effects on cardiovascular system of male rats are not fully understood. The aim of this study was to evaluate the effects of subacute TBT exposure in aorta vascular reactivity from male wistar rats. Rats were randomly divided into three groups: control (C), TBT 500 ng/kg/day and TBT 1000 ng/kg/day. TBT was administered daily for 30 days by oral gavage. We found that TBT exposure enhanced testosterone serum levels and it was also observed obesogenic properties. TBT exposure evoked an increase in endothelium-dependent and independent phenylephrine-induced contraction, associated to an inhibition in eNOS activity. On the other hand, it was observed an enhancement of iNOS and NF-kB protein expression. We also observed an increase in oxidative stress parameters, such as superoxide dismutase (SOD) and catalase expression, and also an increase in malondialdehyde production. Finally, TBT exposure produced aortic intima-media thickness. Taken together, these data suggest a potential cardiovascular toxicological effect after subacute TBT exposure in male rats.
MeSH term(s)	Animals ; Aorta, Thoracic/drug effects ; Aorta, Thoracic/metabolism ; Aorta, Thoracic/pathology ; Aorta, Thoracic/physiopathology ; Lipid Peroxidation/drug effects ; Male ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Muscle, Smooth, Vascular/physiopathology ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Myocytes, Smooth Muscle/pathology ; NF-kappa B/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress/drug effects ; Phosphorylation ; Rats, Wistar ; Testosterone/blood ; Trialkyltin Compounds/toxicity ; Vasoconstriction/drug effects ; Rats
Chemical Substances	NF-kappa B ; Trialkyltin Compounds ; Testosterone (3XMK78S47O) ; tributyltin (4XDX163P3D) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos2 protein, rat (EC 1.14.13.39) ; Nos3 protein, rat (EC 1.14.13.39)
Language	English
Publishing date	2021-12-10
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2021.153067
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Article ; Online: Inosine, an endogenous purine nucleoside, avoids early stages of atherosclerosis development associated to eNOS activation and p38 MAPK/NF-kB inhibition in rats.

Lima, Gabriel Ferreira / Lopes, Rosane de Oliveira / Mendes, Ana Beatriz Araújo / Brazão, Stephani Correia / Autran, Lis Jappour / Motta, Nadia Alice Vieira / Brito, Fernanda C F

European journal of pharmacology

2020 Volume 882, Page(s) 173289

Abstract: Atherosclerosis is a multifactorial chronic disease, initiated by an endothelial dysfunction. Adenosine and its analogs can change a variety of inflammatory diseases and has shown important effects at different disease models. Inosine is a stable ... ...

Abstract	Atherosclerosis is a multifactorial chronic disease, initiated by an endothelial dysfunction. Adenosine and its analogs can change a variety of inflammatory diseases and has shown important effects at different disease models. Inosine is a stable analogous of adenosine, but its effects in inflammatory diseases, like atherosclerosis, have not yet been studied. The aim of this study was to evaluate the pharmacological properties of inosine, administered sub chronically in a hypercholesterolemic model. Male Wistar rats were divided into four groups: control group (C) and control + inosine (C + INO) received standard chow, hypercholesterolemic diet group (HCD) and HCD + inosine (HCD + INO) were fed a hypercholesterolemic diet. At 31st experimentation day, the treatment with inosine was performed for C + INO and HCD + INO groups once daily in the last 15 days. We observed that the hypercholesterolemic diet promoted an increase in lipid levels and inflammatory cytokines production, while inosine treatment strongly decreased these effects. Additionally, HCD group presented a decrease in maximum relaxation acetylcholine induced and an increase in contractile response phenylephrine induced when compared to the control group, as well as it has presented an enhancement in collagen and ADP-induced platelet aggregation. On the other hand, inosine treatment promoted a decrease in contractile response to phenylephrine, evoked an improvement in endothelium-dependent vasorelaxant response and presented antiplatelet properties. Moreover, inosine activated eNOS and reduced p38 MAPK/NF-κB pathway in aortic tissues. Taken together, the present results indicate inosine as a potential drug for the treatment of cardiovascular disorders such as atherosclerosis.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Aorta, Thoracic/drug effects ; Aorta, Thoracic/physiology ; Atherosclerosis/blood ; Atherosclerosis/drug therapy ; Atherosclerosis/metabolism ; Blood Platelets/drug effects ; Blood Platelets/physiology ; Humans ; Inosine/pharmacology ; Inosine/therapeutic use ; Interleukin-6/blood ; Lipid Metabolism/drug effects ; Male ; NF-kappa B/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Rats, Wistar ; Tumor Necrosis Factor-alpha/blood ; Vasodilator Agents/pharmacology ; Vasodilator Agents/therapeutic use ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Il6 protein, rat ; Interleukin-6 ; NF-kappa B ; Platelet Aggregation Inhibitors ; Tumor Necrosis Factor-alpha ; Vasodilator Agents ; Inosine (5A614L51CT) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos3 protein, rat (EC 1.14.13.39) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2020-06-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2020.173289
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Article ; Online: Impact of Brazil Nut (

Saldanha Melo, Henrique / Monnerat, Juliana Arruda de Souza / Costa, Nathalia da Silva / Bento Bernardes, Thais / Magliano, D'Angelo Carlo / Pereira, Aline D'Avila / Almeida, Patricia Pereira / Lima, Gabriel Ferreira / Ferreira de Brito, Fernanda Carla / Stockler Pinto, Milena Barcza / Kindlovits, Raquel / Nogueira, Anna Beatriz / Sepúlveda-Fragoso, Vinicius / Nóbrega, Antonio Claudio Lucas da / Motta, Nadia Alice Vieira da / Medeiros, Renata Frauches

Journal of the American Nutrition Association

2021 Volume 41, Issue 6, Page(s) 559–568

Abstract: Introdution: ...

Abstract	Introdution:
MeSH term(s)	Animals ; Bertholletia/physiology ; Blood Pressure ; Body Composition ; Diet ; Dietary Supplements ; Glucose/pharmacology ; Male ; Rats ; Rats, Wistar
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2769-707X
ISSN (online)	2769-707X
DOI	10.1080/07315724.2021.1925995
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Article ; Online: Impact of Brazil Nut (Bertholletia excelsa, H.B.K.) Supplementation on Body Composition, Blood Pressure, and the Vascular Reactivity of Wistar Rats When Submitted to a Hypersodium Diet

Saldanha Melo, Henrique / Monnerat, Juliana Arruda de Souza / Costa, Nathalia da Silva / Bento Bernardes, Thais / Magliano, D’Angelo Carlo / Pereira, Aline D'Avila / Almeida, Patricia Pereira / Lima, Gabriel Ferreira / Ferreira de Brito, Fernanda Carla / Stockler Pinto, Milena Barcza / Kindlovits, Raquel / Nogueira, Anna Beatriz / Sepúlveda-Fragoso, Vinicius / Nóbrega, Antonio Claudio Lucas da / Motta, Nadia Alice Vieira da / Medeiros, Renata Frauches

Journal of the American Nutrition Association. 2022 Aug. 18, v. 41, no. 6 p.559-568

2022

Abstract: Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis. Objective: The aim of this study was to ... ...

Abstract	Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis. Objective: The aim of this study was to investigate the impact of Brazil nut (Bertholletia excelsa, H.B.K.) (BN) supplementation (10% in chow, wt/wt) on the vascular reactivity of Wistar rats during chronic exposure to a sodium overload (1% in water). Methods: First, male Wistar rats were allocated into two groups: Control Group (CG) and the Hypersodic Group (HG) for 4 weeks. Afterward, the CG was divided into the Brazil Nut Group (BNG) and the HG Group into the Hypersodic Brazil Nut Group (HBNG) for a further 8 weeks, totaling 4 groups. Blood pressure was measured during the protocol. At the end of the protocol, the vascular reactivity procedure was performed. Glucose, lipid profile, lipid peroxidation, and platelet aggregation were analyzed in the serum. Body composition was determined by the carcass technique. Results: The groups that were supplemented with the BN chow presented less body mass gain and body fat mass, together with lower serum glucose levels. The HG Group presented an increase in blood pressure and a higher platelet aggregation, while the BN supplementation was able to blunt this effect. The HG Group also showed an increase in contractile response that was phenylephrine-induced and a decrease in maximum relaxation that was acetylcholine-induced when compared to the other groups. Conclusion: The BN supplementation was able to prevent an impaired vascular function in the early stages of arterial hypertension, while also improving body composition, serum glucose, and platelet aggregation.
Keywords	Bertholletia excelsa ; Brazil nuts ; blood glucose ; blood pressure ; blood serum ; body fat ; body weight ; chronic exposure ; diet ; endothelium ; glucose ; homeostasis ; hypertension ; lipid composition ; lipid peroxidation ; males ; platelet aggregation ; sodium ; Brazil nut ; vascular reactivity ; adiposity
Language	English
Dates of publication	2022-0818
Size	p. 559-568.
Publishing place	Taylor & Francis
Document type	Article ; Online
ISSN	2769-707X
DOI	10.1080/07315724.2021.1925995
Database	NAL-Catalogue (AGRICOLA)

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