scholarly journals Chronic ( − )-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats

2011 ◽  
Vol 106 (9) ◽  
pp. 1337-1348 ◽  
Author(s):  
Manuel Gómez-Guzmán ◽  
Rosario Jiménez ◽  
Manuel Sánchez ◽  
Miguel Romero ◽  
Francisco O'Valle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Human Subjects ◽  
Vascular Wall ◽  
Vascular Lesions ◽  
Intercellular Adhesion Molecule ◽  
No Production ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Status ◽  
Extracellular Signal

The present study analysed the effects of the flavanol ( − )-epicatechin in rats after chronic inhibition of NO synthesis with NG-nitro-l-arginine methyl ester (l-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) l-NAME, (3) l-NAME-epicatechin 2 (l-NAME-Epi 2) and (4) l-NAME-epicatechin 10 (l-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, ( − )-epicatechin 2 or 10 mg/kg. Animals in the l-NAME groups daily received l-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic ( − )-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by l-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, ( − )-epicatechin also increased Akt and eNOS phosphorylation and prevented the l-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF2α) and vascular (dihydroethidium staining, NADPH oxidase activity and p22phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1β and TNFα up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of ( − )-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals Protein carbonyl group content in patients affected by familiar chronic nail candidiasis

2003 ◽  
Vol 12 (4) ◽  
pp. 247-249 ◽  
Author(s):  
S. Gangemi ◽  
A. Saija ◽  
A. Tomaino ◽  
F. Cimino ◽  
R. A. Merendino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Protein Carbonyl ◽  
Intercellular Adhesion Molecule ◽  
Carbonyl Groups ◽  
Intercellular Adhesion Molecule 1 ◽  
Protein Carbonyl Groups ◽  
Halide System ◽  
Reactive Nitrogen Intermediates ◽  
Hands And Feet

Familiar chronic nail candidiasis (FCNC) is a rare disorder characterized by early-onset infections caused by different species of Candida, restricted to the nail of the hands and feet, and associated with a low serum concentration of intercellular adhesion molecule 1. Host defense mechanisms against candidiasis require the cooperation of many immune cells through several candidacidal mechanisms, including oxygen-dependent killing mechanisms, mediated by a superoxide anion radical myeloperoxidase-H2O2-halide system, and reactive nitrogen intermediates. We analyzed protein carbonyl groups (considered a useful marker of oxidative stress) in the serum of patients belonging to a five-generation Italian family with an isolated form of FCNC.Serum protein carbonyl groups in FCNC patients were significantly lower than those measured in healthy donors.Also, if this hypothesis is merely speculative, we could suggest that the decreased circulating level of protein carbonyl groups in these patients is not a marker of a lower oxidative stress condition, but might be linked to a lower protease activity.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

scholarly journals Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 781 ◽  
Author(s):  
Roberta Fusco ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
Tiziana Genovese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Pancreatic Tissue ◽  
Intercellular Adhesion Molecule ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Colon Tissue ◽  
Necrosis Factor Alpha

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

scholarly journals Fibrinogen and fragment D-induced vascular constriction

2005 ◽  
Vol 288 (3) ◽  
pp. H1257-H1264 ◽  
Author(s):  
David Lominadze ◽  
Nina Tsakadze ◽  
Utpal Sen ◽  
Jeff C. Falcone ◽  
Stanley E. D'Souza
Keyword(s):  
Femoral Artery ◽  
Vascular Wall ◽  
Intercellular Adhesion Molecule ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
High Risk Factor ◽  
Arterial Constriction ◽  
Bq 610

Elevated fibrinogen (Fg) concentration in blood is a high risk factor for many cardiovascular diseases. We hypothesize that Fg and its early degradation product, fragment D, may result in arterial constriction by binding endothelial intercellular adhesion molecule-1 (ICAM-1). The vasoconstriction induced by Fg and fragment D was studied in third- and second-order arterioles (3As and 2As, respectively) of Sprague-Dawley rat cremaster muscle in vivo, in aortic and femoral artery rings, and in the segments of first-order arterioles (1As) isolated from rat cremaster muscle. Intravascular infusion of Fg induced significant constriction of 3As and 2As (by 33.4 ± 3.4 and 23.7 ± 4.3%, respectively) in vivo and was abolished in the presence of the specific endothelin type A receptor blocker BQ-610. Fg and fragment D produced significant constriction of both aortic and femoral artery rings. Isolated 1As constricted in response to Fg (0.3 μM) and fragment D (3 μM) by 31 ± 1.4 and 12 ± 1.5%, respectively. Fluorescently labeled Fg and fragment D bound to the vascular wall, whereas albumin bound to a significantly lesser degree. The binding of Fg and fragment D to the arteriolar wall and constriction of aortic and femoral artery rings as well as isolated 1As were abolished in the presence of anti-Fg and anti-ICAM-1 antibodies. These results indicate that binding of Fg and fragment D to the vascular wall through ICAM-1 may contribute to the increased vascular tone and resistance that compromise circulation.

scholarly journals Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation, and organ remodeling

2012 ◽  
Vol 303 (8) ◽  
pp. F1230-F1238 ◽  
Author(s):  
Yuying Liu ◽  
Grant Bledsoe ◽  
Makato Hagiwara ◽  
Bo Shen ◽  
Lee Chao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor ◽  
Nadh Oxidase ◽  
Cardiac Injury ◽  
Thiobarbituric Acid ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Intercellular Adhesion Molecule ◽  
Daily Injection ◽  
Cardiomyocyte Hypertrophy ◽  
Intercellular Adhesion Molecule 1

Kallistatin (KS) levels are reduced in the kidney and blood vessels under oxidative stress conditions. To determine the function of endogenous KS in the renal and cardiovascular systems, KS levels were depleted by daily injection of anti-rat KS antibody into DOCA-salt hypertensive rats for 10 days. Administration of anti-KS antibody resulted in reduced KS levels in the circulation but increased levels of serum thiobarbituric acid reactive substances (an indicator of lipid peroxidation) as well as superoxide formation in the aorta. Moreover, anti-KS antibody injection resulted in increased NADH oxidase activity and superoxide production but decreased nitric oxide levels in the kidney and heart. Endogenous KS blockade aggravated renal dysfunction, damage, hypertrophy, inflammation, and fibrosis as evidenced by decreased creatinine clearance and increased serum creatinine, blood urea nitrogen and urinary protein levels, tubular dilation, protein cast formation, glomerulosclerosis, glomerular enlargement, inflammatory cell accumulation, and collagen deposition. In addition, rats receiving anti-KS antibody had enhanced cardiac injury as indicated by cardiomyocyte hypertrophy, inflammation, myofibroblast accumulation, and fibrosis. Renal and cardiac injury caused by endogenous KS depletion was accompanied by increases in the expression of the proinflammatory genes tumor necrosis factor-α and intercellular adhesion molecule-1 and the profibrotic genes collagen I and III, transforming growth factor-β, and tissue inhibitor of metalloproteinase-1. Taken together, these results implicate an important role for endogenous KS in protection against salt-induced renal and cardiovascular injury in rats by suppressing oxidative stress, inflammation, hypertrophy, and fibrosis.

scholarly journals Intermedin ameliorates vascular and renal injury by inhibition of oxidative stress

2008 ◽  
Vol 295 (6) ◽  
pp. F1735-F1743 ◽  
Author(s):  
Makoto Hagiwara ◽  
Grant Bledsoe ◽  
Zhi-Rong Yang ◽  
Robert S. Smith ◽  
Lee Chao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Urine Volume ◽  
Intercellular Adhesion Molecule ◽  
Protective Agent ◽  
Glomerular Injury ◽  
Intercellular Adhesion Molecule 1 ◽  
Renal Protection

Intermedin (IMD) is a newly discovered peptide related to calcitonin gene-related peptide and adrenomedullin, and has been shown to reduce blood pressure and reactive oxygen species formation in vivo. In this study, we determined whether IMD exerts vascular and renal protection in DOCA-salt hypertensive rats by intravenous injection of adenovirus harboring the human IMD gene. Expression of human IMD was detected in the rat kidney via immunohistochemistry. IMD administration significantly lowered blood pressure, increased urine volume, and restored creatinine clearance. IMD also dramatically decreased superoxide formation and media thickness in the aorta. Vascular injury in the kidney was reduced by IMD gene delivery as evidenced by the prevention of glomerular and peritubular capillary loss. Moreover, IMD lessened morphological damage of the renal tubulointerstitium and reduced glomerular injury and hypertrophy. Attenuation of inflammatory cell accumulation in the kidney by IMD was accompanied by inhibition of p38MAPK activation and intercellular adhesion molecule 1 expression. In addition, IMD gene transfer resulted in a marked decline in myofibroblast and collagen accumulation in association with decreased transforming growth factor-β1 levels. Furthermore, IMD increased nitric oxide excretion in the urine and lowered the amount of lipid peroxidation. These results demonstrate that IMD is a powerful renal protective agent with pleiotropic effects by preventing endothelial cell loss, kidney damage, inflammation, and fibrosis in hypertensive DOCA-salt rats via inhibition of oxidative stress and proinflammatory mediator pathways.

scholarly journals KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction

2019 ◽  
Vol 20 (19) ◽  
pp. 4930 ◽  
Author(s):  
Francesco Vieceli Dalla Sega ◽  
Raffaella Mastrocola ◽  
Giorgio Aquila ◽  
Francesca Fortini ◽  
Claudia Fornelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Loss Of Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Aortic Endothelial

Loss-of-function mutations of the gene encoding Krev interaction trapped protein 1 (KRIT1) are associated with the pathogenesis of Cerebral Cavernous Malformation (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries and affecting 0.5% of the human population. However, growing evidence demonstrates that KRIT1 is implicated in the modulation of major redox-sensitive signaling pathways and mechanisms involved in adaptive responses to oxidative stress and inflammation, suggesting that its loss-of-function mutations may have pathological effects not limited to CCM disease. The aim of this study was to address whether KRIT1 loss-of-function predisposes to the development of pathological conditions associated with enhanced endothelial cell susceptibility to oxidative stress and inflammation, such as arterial endothelial dysfunction (ED) and atherosclerosis. Silencing of KRIT1 in human aortic endothelial cells (HAECs), coronary artery endothelial cells (HCAECs), and umbilical vein endothelial cells (HUVECs) resulted in increased expression of endothelial proinflammatory adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and in enhanced susceptibility to tumor necrosis factor alpha (TNF-α)-induced apoptosis. These effects were associated with a downregulation of Notch1 activation that could be rescued by antioxidant treatment, suggesting that they are consequent to altered intracellular redox homeostasis induced by KRIT1 loss-of-function. Furthermore, analysis of the aorta of heterozygous KRIT1+/− mice fed a high-fructose diet to induce systemic oxidative stress and inflammation demonstrated a 1.6-fold increased expression of VCAM-1 and an approximately 2-fold enhanced fat accumulation (7.5% vs 3.6%) in atherosclerosis-prone regions, including the aortic arch and aortic root, as compared to corresponding wild-type littermates. In conclusion, we found that KRIT1 deficiency promotes ED, suggesting that, besides CCM, KRIT1 may be implicated in genetic susceptibility to the development of atherosclerotic lesions.

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