30-days effects of vildagliptin on vascular function, plasma viscosity, inflammation, oxidative stress, and intestinal peptides on drug-naïve women with diabetes and obesity: a randomized head-to-head metformin-controlled study

CYP450AAM [arachidonic acid metabolites of the CYP450 (cytochrome P450) enzyme system] have a range of biological functions. CYP450AAM are involved in the pathogenesis of hypertension, renal function and vascular function, yet their role in stroke has not been clarified. We aimed at determining the levels of circulating CYP450 metabolites in patients with acute ischaemic stroke (<96 h) compared with healthy age- and gender-matched controls. This was a retrospective case-controlled study of 44 acute ischaemic stroke patients and 44 matched controls. A subset of acute ischaemic stroke patients was available for follow-up. Acute ischaemic stroke patients had elevated plasma CYP450AAM, including 20-HETE (20-hydroxyeicosatetraenoic acid) (1921±170 compared with 1108±170 pmol/l, P<0.001), EETs (epoxyeicosatrienoic acids) (77.88±3.34 compared with 35.35±3.34 nmol/l, P<0.0001) and DiHETEs (dihydroxyeicosatetraenoic acids) (92.87±4.61 compared with 68.17±4.61 nmol/l, P<0.0001), as well as increased plasma F2-isoprostane levels (3754±538 compared with 1947±538 pmol/l, P<0.02), the latter a marker of oxidative stress, compared with controls. In a subset analysis of the stroke patients, plasma 20-HETE, EETs and F2-isoprostanes were attenuated 30 days after the stroke. Baseline 20-HETE levels were also associated with lesion size and functional indices within the stroke patients. The present study highlights the elevation in CYP450AAM and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted.

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Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽

10.3390/molecules26144210 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4210

Author(s):

Yan Zhou ◽

Chunxiu Zhou ◽

Xutao Zhang ◽

Chi Teng Vong ◽

Yitao Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Vascular Function ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Ex Vivo ◽

Diabetic Mice ◽

And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

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Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study

BMJ Open ◽

10.1136/bmjopen-2020-041500 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041500

Author(s):

Zoe Menczel Schrire ◽

Craig L Phillips ◽

Shantel L Duffy ◽

Nathaniel S Marshall ◽

Loren Mowszowski ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Feasibility Trial ◽

Controlled Study ◽

Brain Oxidative Stress ◽

Randomised Controlled

IntroductionMelatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysisThe study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and disseminationThis protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol versionV.8 15 October 2020.

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GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽

10.3390/antiox10081175 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1175

Author(s):

Johanna Helmstädter ◽

Karin Keppeler ◽

Franziska Aust ◽

Leonie Küster ◽

Katie Frenis ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Function ◽

Vascular Inflammation ◽

Cecal Ligation ◽

Isometric Tension ◽

Polymicrobial Sepsis ◽

Dot Blot ◽

Markers Of Inflammation ◽

Anti Inflammatory ◽

And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

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Effects of heat-not-burn compared to combustible cigarettes on coronary flow, myocardial work index and vascular function

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.098 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

I Ikonomidis ◽

K Katogiannis ◽

D Vlastos ◽

G Kostelli ◽

K Kourea ◽

...

Keyword(s):

Oxidative Stress ◽

Platelet Activation ◽

Vascular Function ◽

Coronary Flow ◽

Arterial Compliance ◽

Chronic Phase ◽

Protein Carbonyls ◽

Flow Reserve ◽

Work Index ◽

Chronic Study

Abstract Funding Acknowledgements Type of funding sources: None. Aim/Introduction: Heat-not-burn cigarette (HNBC) constitutes a non-combustible smoke product. Purpose We compare the effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function, platelet activation and oxidative stress. Methods We compared the effects of HNBC to those of tobacco cigarette (TCig), on arterial stiffness, oxidative stress, and platelet activation, acutely and after 1 month of switching to HNBC, as well as on endothelial, myocardial, and coronary function after 1 month of switching to HNBC. In the acute study, 50 smokers were randomized into smoking a single Tcig or an HNBC and after 60 minutes were crossed over to the alternate smoking (HNBC or Tcig). For the chronic phase, 75 smokers were examined. Of those, 50 were switched to HNBC and 25 continued Tcig for 1 month. Pulse wave velocity (PWV) and biomarkers [malondialdehyde (MDA), protein carbonyls (PC), and thromboxane B2 (TXB2)] were assessed in the acute and chronic study. Myocardial deformation [global longitundinal strain (GLS), myocardial work index (GWI) and wasted myocardial work (GWW)], coronary flow reserve (CFR) by Doppler echocardiography, total arterial compliance (TAC), and flow-mediated dilation (FMD) were additionally assessed in the chronic study. Results Compared to baseline, TCig smoking acutely increased exhaled CO, PWV, MDA, and TxB2 (p < 0.05), while no changes were observed after HNBC. Compared to resuming Tcig smoking, switching to HNBC for 1 month improved CO (mean change: -55% vs -2.4%), FMD ( +55% vs +15%), CFR (+46% vs +4%), TAC (+9% vs -0.5%), GLS (+6% vs +1%), GWW (-19% vs +0.5%), MDA (-19% vs 1 %), and TxB2 (-12% vs 4%) (p < 0.05 for all comparisons). Conclusions HNBCs exert a less detrimental effect on vascular, cardiac and platelet function than combustible tobacco.

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Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1186/s43088-020-00092-6 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Theresa Chikopela ◽

Douglas C. Heimburger ◽

Longa Kaluba ◽

Pharaoh Hamambulu ◽

Newton Simfukwe ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Endothelial Dysfunction ◽

Body Mass ◽

Vascular Function ◽

Aortic Ring ◽

Normal Weight ◽

Oxide Synthase ◽

Weight Groups

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

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Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences ◽

10.3390/ijms22031296 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1296

Author(s):

Yue Ruan ◽

Subao Jiang ◽

Adrian Gericke

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Vascular Function ◽

Vascular Dysfunction ◽

Therapeutic Strategies ◽

Vision Impairment ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study

American Journal of Psychiatry ◽

10.1176/appi.ajp.2007.07010079 ◽

2008 ◽

Vol 165 (3) ◽

pp. 352-358 ◽

Cited By ~ 127

Author(s):

Ren-Rong Wu ◽

Jing-Ping Zhao ◽

Xiao-Feng Guo ◽

Yi-Qun He ◽

Mao-Sheng Fang ◽

...

Keyword(s):

Weight Gain ◽

Controlled Study ◽

First Episode ◽

Double Blind ◽

Double Blind Placebo ◽

Drug Naïve ◽

First Episode Schizophrenia

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Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0578 ◽

2017 ◽

Vol 95 (12) ◽

pp. 1406-1413 ◽

Cited By ~ 2

Author(s):

Esra Aycan-Ustyol ◽

Merve Kabasakal ◽

Seldag Bekpinar ◽

F. Ilkay Alp-Yıldırım ◽

Ozge Tepe ◽

...

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Vascular Function ◽

Asymmetric Dimethylarginine ◽

Vascular Dysfunction ◽

Cardiovascular Complication ◽

Heme Oxygenase 1 ◽

Antioxidant Enzyme Activities ◽

Symmetric Dimethylarginine ◽

Inflammatory Changes

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase 1 HO-1) induction influenced kidney and vascular function in GM-administered rats. GM (100 mg·kg–1·day–1; i.p.) was given to rats alone or together with hemin (20 mg·kg–1 on alternate days; i.p.) for 14 days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathological examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme activities and l-arginine levels in the kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, or creatinine levels. We conclude that HO-1 induction may be effective in improving renal oxidative stress, inflammation, and vascular dysfunction mediated by GM.

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The role of oxidative stress in the cardiovascular actions of particulate air pollution

Biochemical Society Transactions ◽

10.1042/bst20140090 ◽

2014 ◽

Vol 42 (4) ◽

pp. 1006-1011 ◽

Cited By ~ 49

Author(s):

Mark R. Miller

Keyword(s):

Oxidative Stress ◽

Air Pollution ◽

Diesel Exhaust ◽

Vascular Function ◽

Cardiovascular Effects ◽

Increase Blood Pressure ◽

Potential Mechanism ◽

Particulate Air Pollution ◽

Cardiovascular Actions

Air pollution has been estimated to be responsible for several millions of deaths worldwide per year, the majority of which have been attributed to cardiovascular causes. The particulate matter in air pollution has been shown impair vascular function, increase blood pressure, promote thrombosis and impair fibrinolysis, accelerate the development of atherosclerosis, increase the extent of myocardial ischaemia, and increase susceptibility to myocardial infarction. The pathways underlying these effects are complex and poorly understood; however, particulate-induced oxidative stress repeatedly emerges as a potential mechanism in all of these detrimental cardiovascular actions. The present mini-review will use diesel exhaust as an example of a pollutant rich in combustion-derived nanoparticles, to describe the potential by which oxidative stress could drive the cardiovascular effects of air pollution.

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