scholarly journals Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Saher F. Ali ◽  
Owen L. Woodman
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Endothelial Function ◽  
Xanthine Oxidase ◽  
Palm Oil ◽  
Oxidant Stress ◽  
Rat Aorta ◽  
Isolated Aorta ◽  
Oil Extract ◽  
Endothelium Dependent Relaxation

Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect ofα-tocopherol,α-,δ-, andγ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin andα-tocopherol were more effective in the isolated aorta. Tocomin andα-tocopherol restored endothelial function in the presence of oxidant stress butα-,δ-, andγ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without,α-tocopherol. Tocotrienol rich tocomin is more effective thanα-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and althoughα-,δ-, andγ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function.

IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation

2000 ◽  
Vol 279 (4) ◽  
pp. H1555-H1562 ◽  
Author(s):  
Carol A. Gunnett ◽  
Donald D. Heistad ◽  
Daniel J. Berg ◽  
Frank M. Faraci
Keyword(s):  
Endothelial Function ◽  
Xanthine Oxidase ◽  
Carotid Arteries ◽  
Interleukin 10 ◽  
Vehicle Injection ◽  
Endothelium Dependent Relaxation ◽  
Deficient Mice ◽  
Lps Treatment

Little is known about the role of interleukin-10 (IL-10), an anti-inflammatory cytokine, in blood vessels. We used IL-10-deficient mice (IL-10 −/−) to examine the hypothesis that IL-10 protects endothelial function after lipopolysaccharide (LPS) treatment. The responses of carotid arteries were studied in vitro 6 h after injection of a relatively low dose of LPS (10 μg ip). In IL-10 −/− mice, the maximum relaxation to ACh (3 μM) was 56 ± 6% (means ± SE) after LPS injection and 84 ± 4% after vehicle injection ( P < 0.05). Thus endothelium-dependent relaxation was impaired in carotid arteries from IL-10 −/− mice after LPS injection. In contrast, this dose of LPS did not alter relaxation to ACh in vessels from wild-type (IL-10 +/+) mice. Relaxation to nitroprusside and papaverine was similar in arteries from both IL-10 −/− and IL-10 +/+ mice after vehicle or LPS injection. Because inflammation is associated with increased levels of reactive oxygen species, we also tested the hypothesis that superoxide contributes to the impairment of endothelial function by LPS in the absence of IL-10. Results using confocal microscopy and hydroethidine indicated that levels of superoxide are elevated in carotid arteries from IL-10 −/− mice compared with IL-10 +/+ mice after LPS injection. The impaired relaxation of arteries from IL-10 −/− mice after LPS injection was restored to normal by polyethylene glycol-suspended superoxide dismutase (50 U/ml) or allopurinol (1 mM), an inhibitor of xanthine oxidase. These data provide direct evidence that IL-10 protects endothelial function after an acute inflammatory stimulus by limiting local increases in superoxide. The source of superoxide in this model may be xanthine oxidase.

Luteolin reduces high glucose-mediated impairment of endothelium-dependent relaxation in rat aorta by reducing oxidative stress

2010 ◽  
Vol 61 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Ling-Bo Qian ◽  
Hui-Ping Wang ◽  
Ying Chen ◽  
Fang-Xia Chen ◽  
Yan-Yan Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Rat Aorta ◽  
Endothelium Dependent Relaxation

scholarly journals Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Diabetologia ◽  
1995 ◽  
Vol 38 (12) ◽  
pp. 1475-1478 ◽  
Author(s):  
A. Keegan ◽  
H. Walbank ◽  
M. A. Cotter ◽  
N. E. Cameron
Keyword(s):  
Vitamin E ◽  
Rat Aorta ◽  
Diabetic Rat ◽  
Endothelium Dependent Relaxation

P3493Uremic toxin induced endothelial dysfunction can be restored by inhibition of the aryl hydrocarbon receptor: implications for cardiovascular disease treatment in chronic kidney disease patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kompa ◽  
C Nguyen ◽  
A J Edgley ◽  
D J Kelly
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Aryl Hydrocarbon Receptor ◽  
Uremic Toxin ◽  
Aryl Hydrocarbon ◽  
Endothelium Dependent Relaxation

Abstract Introduction Cardiovascular disease (CVD) mortality is significantly higher in chronic kidney disease (CKD) patients, with vascular calcification and atherosclerosis proving to be major contributors. Endothelial dysfunction is an early marker of atherosclerosis, triggered by oxidative stress and reduced nitric oxide production. The uremic toxin indoxyl sulphate (IS), a protein-bound non-dialyzable molecule derived from dietary tryptophan that accumulates in the blood of CKD patients, activates the aryl hydrocarbon receptor (AhR) promoting downstream cytochrome P450 1A1 (CYP1A1) expression mediating oxidative stress and potentially endothelial dysfunction. Targeting IS-induced AhR activation in the endothelium has not previously been examined and may represent a novel approach in targeting endothelial dysfunction. Purpose To assess the ability of the AhR antagonist, CH223191, to inhibit IS-mediated impairment of endothelial function and disruption of redox balance. Methods To assess endothelium-dependent relaxation, the thoracic aorta from adult male Sprague Dawley rats (N=10) were used in ex vivo experiments. Rings (5mm) from the aorta were exposed to IS (300μM) in the presence and absence of the AhR antagonist CH223191 (1 and 10μM), prior to pre-constriction of the vessel with phenylephrine (30μM) followed by relaxation with acetylcholine (ACh; 1nM-30μM). Control rings were not exposed to IS or CH223191 to determine normal endothelial responses to ACh. Responses were recorded with isometric force transducers connected to a PowerLab using Chart Software. Tissue sections from these rings were stained for superoxide using dihydroethidium. To examine key AhR-mediated oxidative stress pathways, separate aortic rings were exposed to IS and CH223191, under the above conditions, for 4 hours prior to RNA extraction and real-time PCR analysis. Results IS reduced the maximum level of endothelium-dependent relaxation (Rmax) to 50.17±2.71% (P<0.001) compared to control (86.00±3.93%). In the presence of IS, CH223191 restored Rmax to 77.74±3.14% (1μM) and 81.63±3.27% (10μM) (Figure, P<0.001). The potency of ACh, known as the pEC50 (negative logarithm of the effective concentration of ACh to produce a relaxation response of 50%), in control tissues (−7.08±0.07) was increased 100-fold following exposure of IS (−5.10±0.13; P<0.001). CH223191 restored pEC50 back to control values (1μM, −6.62±0.09; 10μM, −6.83±0.08; P<0.05). IS-exposed rings increased superoxide expression (P<0.001) and CYP1A1 gene expression (P<0.001), CH223191 restored expression of both superoxide (P<0.001) and CYP1A1 (P<0.001) back to control levels. CH223191 restores endothelial function Conclusion Our findings demonstrate the adverse impact of IS-mediated AhR activation on the vascular endothelium, where oxidative stress may play a critical role inducing endothelial dysfunction in the vasculature of the heart and kidneys. AhR inhibition may provide a novel therapy for CVD in the CKD setting. Acknowledgement/Funding National Health and Medical Research Council of Australia Program Grant

Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress

2009 ◽  
Vol 616 (1-3) ◽  
pp. 200-205 ◽  
Author(s):  
Bi-hui Jin ◽  
Ling-bo Qian ◽  
Shuai Chen ◽  
Jun Li ◽  
Hui-ping Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Aorta ◽  
Endothelium Dependent Relaxation

Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs

2006 ◽  
Vol 290 (3) ◽  
pp. R609-R615 ◽  
Author(s):  
Elena Daghini ◽  
Alejandro R. Chade ◽  
James D. Krier ◽  
Daniele Versari ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Endothelial Function ◽  
Sodium Nitroprusside ◽  
Xanthine Oxidase ◽  
Oxidized Ldl ◽  
Renal Hemodynamics ◽  
Plasma Uric Acid ◽  
Before And After ◽  
Cortical Perfusion

Hypercholesterolemia (HC), a major risk factor for onset and progression of renal disease, is associated with increased oxidative stress, potentially causing endothelial dysfunction. One of the sources of superoxide anion is xanthine oxidase (XO), but its contribution to renal endothelial function in HC remains unclear. We tested the hypothesis that XO modulates renal hemodynamics and endothelial function in HC pigs. Four groups ( n = 23) of female domestic pigs were studied 12 wk after either normal ( n = 11) or HC diet ( n = 12). Oxidative stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting and immunohistochemistry). Renal hemodynamics and function were studied with electron beam-computed tomography before and after endothelium-dependent (ACh) and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal infusion of either oxypurinol or saline ( n = 5–6 in each group). HC showed elevated oxidative stress, higher plasma uric acid (23.8 ± 3.8 vs. 6.2 ± 0.8 μM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO expression compared with normal. Inhibition of XO in HC significantly improved the blunted responses to ACh of cortical perfusion (13.5 ± 12.1 and 37.2 ± 10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood flow, and glomerular filtration rate; restored medullary perfusion; and improved the blunted cortical perfusion response to sodium nitroprusside. This study demonstrates that the endogenous XO system is activated in swine HC. Furthermore, it suggests an important role for XO in regulation of renal hemodynamics, function, and endothelial function in experimental HC.

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