Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability

Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.

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Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661027 ◽

1984 ◽

Vol 51 (01) ◽

pp. 089-092 ◽

Cited By ~ 24

Author(s):

M A Boogaerts ◽

J Van de Broeck ◽

H Deckmyn ◽

C Roelant ◽

J Vermylen ◽

...

Keyword(s):

Vitamin E ◽

Protective Effect ◽

Umbilical Vein ◽

Endothelial Damage ◽

Endothelial Injury ◽

Mediated Effects ◽

Anti Oxidant ◽

Endothelial Cell Cultures ◽

Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

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Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Biomedicines ◽

10.3390/biomedicines9080965 ◽

2021 ◽

Vol 9 (8) ◽

pp. 965

Author(s):

Grazia Maugeri ◽

Agata Grazia D’Amico ◽

Salvatore Saccone ◽

Concetta Federico ◽

Daniela Maria Rasà ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Epithelial Mesenchymal Transition ◽

Human Cancer ◽

Matrix Metalloproteinase 2 ◽

Mesenchymal Transition ◽

Hypoxic Area ◽

Vitro Model ◽

Human Gbm ◽

Endothelial Growth Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

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Peptide-derived from Seahorse Exerts a Protective Effect against Cholinergic Neuronal Death in in vitro Model of Alzheimer's Disease

Procedia Chemistry ◽

10.1016/j.proche.2015.03.047 ◽

2015 ◽

Vol 14 ◽

pp. 343-352 ◽

Cited By ~ 2

Author(s):

Ratih Pangestuti ◽

Se-Kwon Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protective Effect ◽

Neuronal Death ◽

In Vitro Model ◽

Model Of Alzheimer’S Disease ◽

Vitro Model

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Molecular mechanisms involved in the protective effect of pituitary adenylate cyclase-activating polypeptide in an in vitro model of amyotrophic lateral sclerosis

Journal of Cellular Physiology ◽

10.1002/jcp.27328 ◽

2018 ◽

Vol 234 (4) ◽

pp. 5203-5214 ◽

Cited By ~ 11

Author(s):

Grazia Maugeri ◽

Agata G. D’Amico ◽

Daniela M. Rasà ◽

Concetta Federico ◽

Salvatore Saccone ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Adenylate Cyclase ◽

Protective Effect ◽

In Vitro Model ◽

Molecular Mechanisms ◽

Pituitary Adenylate Cyclase ◽

Vitro Model ◽

Lateral Sclerosis

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Protective effect of triflusal and its main metabolite HTB in an in vitro model of anoxia-reoxygenation in rat brain slices: comparison with acetylsalicylic and salicylic acids

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-004-1001-y ◽

2004 ◽

Vol 371 (1) ◽

pp. 81-88 ◽

Cited By ~ 5

Author(s):

J. A. González-Correa ◽

M. M. Arrebola ◽

I. M. Ureña ◽

D. Ruiz-Villafranca ◽

J. Muñoz-Marín ◽

...

Keyword(s):

Protective Effect ◽

Rat Brain ◽

In Vitro Model ◽

Brain Slices ◽

Main Metabolite ◽

Vitro Model ◽

Salicylic Acids

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The Mouse Liver Slice System as an In Vitro Model for Testing the Protective Effect of N-Acetylcysteine Against Hepatotoxic Agents

Toxicology Methods ◽

10.3109/15376519109036526 ◽

1991 ◽

Vol 1 (1) ◽

pp. 66-74

Author(s):

Uri Wormser ◽

Simone Ben-zakine

Keyword(s):

Protective Effect ◽

Mouse Liver ◽

In Vitro Model ◽

Liver Slice ◽

Vitro Model

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Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model

Human & Experimental Toxicology ◽

10.1177/0960327111433901 ◽

2012 ◽

Vol 31 (8) ◽

pp. 788-797 ◽

Cited By ~ 30

Author(s):

M Singh ◽

P Sasi ◽

V H Gupta ◽

G Rai ◽

D N Amarapurkar ◽

...

Keyword(s):

Protective Effect ◽

In Vitro Model ◽

Antitubercular Drug ◽

Drug Induced ◽

Vitro Model

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Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes

Journal of the American Society of Nephrology ◽

10.1681/asn.v125993 ◽

2001 ◽

Vol 12 (5) ◽

pp. 993-1000 ◽

Cited By ~ 4

Author(s):

AN S. DE VRIESE ◽

RONALD G. TILTON ◽

MARLIES ELGER ◽

CLIFFORD C. STEPHAN ◽

WILHELM KRIZ ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Renal Dysfunction ◽

Diabetic Rats ◽

Renal Physiology ◽

Vascular Endothelial ◽

Binding Studies ◽

Anti Vegf ◽

Endothelial Growth Factor

Abstract. Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell typesin vitroand in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based onin vitrobinding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.

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