Dietary nitrate supplementation prevents radiotherapy-induced xerostomia.
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ABSTRACT:
SUBMITTER: Feng X
PROVIDER: S-EPMC8563005 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The purpose of this study is to determine whether dietary nitrate supplementation improves performance in cardiopulmonary exercise testing (CPET).
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Project description:The aim of this study was to test the hypothesis that long-term dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving ventricular function and reducing mitochondrial respiratory chain damage.Doxorubicin is a powerful anthracycline antibiotic used to treat divergent human neoplasms. Its clinical use is limited because of severe cardiotoxic side effects. Dietary nitrate and nitrite are essential nutrients for maintenance of steady-state tissue levels of nitric oxide and may play a therapeutic role in diseases associated with nitric oxide insufficiency or dysregulation. Dietary nitrate and nitrite supplementation alleviates myocardial injury caused by ischemia-reperfusion and cardiac arrest-resuscitation.Adult male CF-1 mice were given a single dose of doxorubicin (15 mg/kg intraperitoneally), and left ventricular contractile function was assessed 5 days later using both echocardiography and pressure-volume Millar catheterization. A nitrate supplementation regimen (1 g/l sodium nitrate in drinking water) was started 7 days before doxorubicin injection and continued thereafter. Cardiomyocyte necrosis and apoptosis, tissue lipid peroxidation, and plasma nitrate and nitrite levels were assessed. In addition, mitochondrial complex I activity, oxidative phosphorylation capacity, and hydrogen peroxide generation were determined in parallel experiments.Doxorubicin caused impairment of ventricular contractility and cell death, which were significantly reduced by nitrate supplementation (p < 0.05). These cardioprotective effects were associated with a significant decrease in tissue lipid peroxidation. Nitrate supplementation significantly preserved mitochondrial complex I activity and oxidative phosphorylation and attenuated hydrogen peroxide generation after doxorubicin treatment.Long-term oral intake of inorganic nitrate attenuates doxorubicin-induced ventricular dysfunction, cell death, oxidative stress, and mitochondrial respiratory chain damage. Nitrate could be a promising therapeutic agent against doxorubicin-induced cardiotoxicity.
| S-EPMC4127335 | biostudies-literature
Project description:PurposeDespite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients.MethodsFifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake.ResultsHigher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake.ConclusionRadiation-induced xerostomia increased the frequency of CFB intake.
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Project description:Oleocanthal (OLE), a characteristic and exclusive secoiridoid of Oleoaceae family, is mainly found in extra virgin olive oil (EVOO). Previous studies have reported its antioxidant, anti-inflammatory, antimicrobial, anticancer and neuroprotective effects. Since the pathogenesis of rheumatoid arthritis (RA) involves inflammatory and oxidative components, this study was designed to evaluate the preventive role of dietary OLE-supplemented effects in collagen-induced arthritis (CIA) murine model. Animals were fed with a preventive OLE-enriched dietary during 6 weeks previous to CIA induction and until the end of experiment time. At day 43 after first immunization, mice were sacrificed: blood was recollected and paws were histological and biochemically processed. Dietary OLE prevented bone, joint and cartilage rheumatic affections induced by collagen. Levels of circulatory matrix metalloproteinase (MMP)-3 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17, IFN-γ) were significantly decreased in secoiridoid fed animals. Besides, dietary OLE was able to diminish COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms underlying these protective effects could be related to Nrf-2/HO-1 axis activation and the inhibition of relevant signaling pathways including JAK-STAT, MAPKs and NF-κB, thus controlling the production of inflammatory and oxidative mediators. Overall, our results exhibit preliminary evidences about OLE, as a novel dietary tool for the prevention of autoimmune and inflammatory disorders, such as RA.
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Project description:Key pointsRespiratory muscle function declines with ageing, contributing to breathing complications in the elderly. Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO3 for 14 days compared with age-matched controls. Myofibrillar protein phosphorylation, which enhances contractile function, did not change in our study - a finding inconsistent with the hypothesis that this post-translational modification is a mechanism for dietary nitrate to improve muscle contractile function. Nitrate supplementation did not change the abundance of calcium-handling proteins in the diaphragm of old mice, in contrast with findings from the limb muscles of young mice in previous studies. Our findings suggest that nitrate supplementation enhances myofibrillar protein function without affecting the phosphorylation status of key myofibrillar proteins.AbstractInspiratory muscle (diaphragm) function declines with age, contributing to ventilatory dysfunction, impaired airway clearance, and overall decreased quality of life. Diaphragm isotonic and isometric contractile properties are reduced with ageing, including maximal specific force, shortening velocity and peak power. Contractile properties of limb muscle in both humans and rodents can be improved by dietary nitrate supplementation, but effects on the diaphragm and mechanisms behind these improvements remain poorly understood. One potential explanation underlying the nitrate effects on contractile properties is increased phosphorylation of myofibrillar proteins, a downstream outcome of nitrate reduction to nitrite and nitric oxide. We hypothesized that dietary nitrate supplementation would improve diaphragm contractile properties in aged mice. To test our hypothesis, we measured the diaphragm function of old (24 months) mice allocated to 1 mm NaNO3 in drinking water for 14 days (n = 8) or untreated water (n = 6). The maximal rate of isometric force development (∼30%) and peak power (40%) increased with nitrate supplementation (P < 0.05). There were no differences in the phosphorylation status of key myofibrillar proteins and abundance of Ca2+-release proteins in nitrate vs. control animals. In general, our study demonstrates improved diaphragm contractile function with dietary nitrate supplementation and supports the use of this strategy to improve inspiratory function in ageing populations. Additionally, our findings suggest that dietary nitrate improves diaphragm contractile properties independent of changes in abundance of Ca2+-release proteins or phosphorylation of myofibrillar proteins.
| S-EPMC10195135 | biostudies-literature
Project description:To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity.
| S-EPMC6983433 | biostudies-literature
Project description:This study tested the hypothesis that glycine improves intestinal barrier function through regulating oxidative stress in broilers exposed to heat stress. A total of 300 twenty-one-day-old female Arbor Acres broilers (600 ± 2.5g) was randomly allocated to 5 treatments (6 replicate of 10 birds each). The 5 treatments were as follows: the control group (CON) was kept under thermoneutral condition (24 ± 1°C) and was fed a basal diet. Broilers fed a basal diet and reared under high ambient temperature (HT) were considered as the HT group (34 ± 1°C for 8 h/d). Broilers fed a basal diet supplemented with 0.5%, 1.0%, and 2.0% glycine and exposed to HT were regarded as the HT + glycine treatments. The results exhibited that heat stress reduced growth performance, serum total antioxidant capacity (T-AOC), and glutathione (GSH) concentration (P < 0.05); increased activity of serum catalase (CAT) and the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) (P < 0.05). HT exposure led to downregulating the mRNA expression of NAD(P)H quinone dehydrogenase 1 (NQO1), Occludin, and zonula occludens-1 (ZO-1) (P < 0.05); enhanced the mRNA levels of Kelch-like ECH-associated protein 1 (Keap1), CAT, glutathione synthetase (GSS), and glutamate-cysteine ligase modifier subunit (GCLM) (P < 0.05); impaired the intestinal morphology (P < 0.05); and altered the diversity and community of gut microbiota (P < 0.05). The final body weight (FBW), ADFI, ADG, and gain-to-feed ratio (G: F) increased linearly or quadratically, and the antioxidant capacity was improved (P < 0.05) with glycine supplementation. Glycine treatment increased the villus height (VH), and villus height to crypt depth ratio (V/C) of the duodenum linearly or quadratically, and linearly increased the VH of jejunum and ileum. The mRNA expression of Occludin, and ZO-1 were increased linearly in the ileum mucosa of broilers subjected to HT. Collectively, these results demonstrated that glycine supplementation alleviates heat stress-induced dysfunction of antioxidant status and intestinal barrier in broilers.
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Project description:In the United States, latest projections indicate the number of adults 65 years of age and older is expected to double by 2050. Given that increased oxidative stress is a hallmark of aging, it is understandable that waning nitric oxide and chronic degenerative disease arise in tandem. To this end, translational evidence-based strategies are needed to mitigate the impending toll on personal and public health. Dietary nitrate supplementation, particularly in the form of beetroot juice, is an active area of inquiry that has gained considerable attention in recent years. Compelling evidence has revealed beetroot juice can elicit potent physiological responses that may offer associated health benefits for multiple clinical disorders including hypertension, dementia, and sarcopenia. Even in the absence of overt disease, age-related impairments in cardiovascular and skeletal muscle function may uniquely benefit from beetroot juice supplementation as evidence has shown blood pressure lowering effects and improved muscle function/contractility - presumably from increased nitric oxide bioavailability. This, in turn, presents a practical opportunity for susceptible populations to support ease of movement and exercise tolerance, both of which may promote free-living physical activity. A theoretical rationale details the potential health effects of dietary nitrate supplementation, wherein a working framework hypothesizes beetroot juice consumption prior to structured exercise training may offer synergistic benefits to aid healthy aging and independent-living among older adults.
| S-EPMC7313402 | biostudies-literature
Project description:Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1-/- adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.
| S-EPMC6004437 | biostudies-literature
Project description:Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer (OPC). Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. This prospective study enrolled OPC patients treated between 2016 and 2018 in three centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the EORTC H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before RT, after receiving 20 Gy and within 24 hours after treatment completion. qPCR arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiotherapy had AUC 0.96 (95% CI: 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (AUC 0.90 (95% CI: 0.75-1.00)). These results were confirmed in the validation group. In the validation group pre-radiotherapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same two miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose, yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6 % sensitivity and 55.2 % specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0 % sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0 % sensitivity and 58.6 % specificity. Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiotherapy or during therapy (after 20 Gy) had a significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from the one related to the dosimetric data.
2021-08-16 | GSE182178 | GEO