Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers

Hwang, Chueh‐Lung; Bian, Jing-Tan; Hill, Joshua A.; Peters, Tara; Piano, Mariann R.; Phillips, Shane A.

doi:10.1111/acer.14254

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…The enzyme DHFR depends on FA levels, connecting with the lower FA hepatic deposits found in these animals [ 58 ]. BH4 depletion is the main cause of the eNOS uncoupling process [ 59 ], even in adolescents exposed to high amounts of EtOH [ 60 ]. It is transformed to its inactive form BH2 in pro-oxidant ambients, such as that which is generated in the liver during BD exposure.…”

Section: Discussionmentioning

confidence: 99%

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking

et al. 2022

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Chronic ethanol consumption and liver disease are intimately related to folic acid (FA) homeostasis. Despite the fact that FA decreases lipid oxidation, its mechanisms are not yet well elucidated. Lately, adolescents have been practising binge drinking (BD), consisting of the intake of a high amount of alcohol in a short time; this is a particularly pro-oxidant form of consumption. The aim of this study is to examine, for the first time, FA homeostasis in BD adolescent rats and its antioxidant properties in the liver. We used adolescent rats, including control rats and rats exposed to an intermittent intraperitoneal BD model, supplemented with or without FA. Renal FA reabsorption and renal FA deposits were increased in BD rats; hepatic deposits were decreased, and heart and serum levels remained unaffected. This depletion in the liver was accompanied by higher transaminase levels; an imbalance in the antioxidant endogenous enzymatic system; lipid and protein oxidation; a decrease in glutathione (GSH) levels; hyper-homocysteinemia (HHcy); an increase in NADPH oxidase (NOX) 1 and NOX4 enzymes; an increase in caspase 9 and 3; and a decrease in the anti-apoptotic metallopeptidase inhibitor 1. Furthermore, BD exposure increased the expression of uncoupled endothelial nitric oxide synthase (eNOS) by increasing reactive nitrogen species generation and the nitration of tyrosine proteins. When FA was administered, hepatic FA levels returned to normal levels; transaminase and lipid and protein oxidation also decreased. Its antioxidant activity was due, in part, to the modulation of superoxide dismutase activity, GSH synthesis and NOX1, NOX4 and caspase expression. FA reduced HHcy and increased the expression of coupled eNOS by increasing tetrahydrobiopterin expression, avoiding nitrosative stress. In conclusion, FA homeostasis and its antioxidant properties are affected in BD adolescent rats, making it clear that this vitamin plays an important role in the oxidative, nitrosative and apoptotic hepatic damage generated by acute ethanol exposure. For this, FA supplementation becomes a potential BD therapy for adolescents, preventing future acute alcohol-related harms.

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Section: Discussionmentioning

confidence: 99%

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking

et al. 2022

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“…As previously described [ 29 ], microvascular endothelial function was assessed using flow-induced dilation (FID) in arterioles isolated from subcutaneous adipose tissue of participants. Briefly, participants received subcutaneous fat biopsy with sterile techniques performed by a trained clinician.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Low-Carbohydrate Diet on Macrovascular and Microvascular Endothelial Function Is Not Affected by the Provision of Caloric Restriction in Women with Obesity: A Randomized Study

et al. 2020

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Obesity impairs both macro- and microvascular endothelial function due to decreased bioavailability of nitric oxide. Current evidence on the effect of low-carbohydrate (LC) diet on endothelial function is conflicting and confounded by the provision of caloric restriction (CR). We tested the hypothesis that LC without CR diet, but not LC with CR diet, would improve macro- and microvascular endothelial function in women with obesity. Twenty-one healthy women with obesity (age: 33 ± 2 years, body mass index: 33.0 ± 0.6 kg/m2; mean ± SEM) were randomly assigned to receive either a LC diet (~10% carbohydrate calories) with CR (n = 12; 500 calorie/day deficit) or a LC diet without CR (n = 9) and completed the 6-week diet intervention. After the intervention, macrovascular endothelial function, measured as brachial artery flow-mediated dilation did not change (7.3 ± 0.9% to 8.0 ± 1.1%, p = 0.7). On the other hand, following the LC diet intervention, regardless of CR, blocking nitric oxide production decreased microvascular endothelial function, measured by arteriolar flow-induced dilation (p ≤ 0.02 for both diets) and the magnitude was more than baseline (p ≤ 0.04). These data suggest improved NO contributions following the intervention. In conclusion, a 6-week LC diet, regardless of CR, may improve microvascular, but not macrovascular endothelial function, via increasing bioavailability of nitric oxide in women with obesity.

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“…Ethanol consumption promotes BH 4 deficiency, which occurs in parallel to an impaired eNOS-dependent vasodilatation [86,87]. An in-vivo study showed that, in the microcirculation, ethanol consumption compromises endothelium-dependent vasorelaxation and this response is reversed by administration of BH 4 , suggesting a role for uncoupled eNOS in this response [88]. This is indirect evidence that suggests a possible contribution of uncoupled eNOS to ROS generation induced by ethanol.…”

Section: Other Sources Of Ethanol-induced Ros Generation In the Vascu...mentioning

confidence: 96%

Reactive Oxygen Species Are Central Mediators of Vascular Dysfunction and Hypertension Induced by Ethanol Consumption

Padovan,

Dourado,

Pimenta

et al. 2023

Antioxidants

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Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature trigger important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin–angiotensin–aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS, and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.

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Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers

Cited by 8 publications

References 39 publications

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking

The Effect of Low-Carbohydrate Diet on Macrovascular and Microvascular Endothelial Function Is Not Affected by the Provision of Caloric Restriction in Women with Obesity: A Randomized Study

Reactive Oxygen Species Are Central Mediators of Vascular Dysfunction and Hypertension Induced by Ethanol Consumption

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