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1.
The Role of Sirtuins in Antioxidant and Redox Signaling.
Singh, CK, Chhabra, G, Ndiaye, MA, Garcia-Peterson, LM, Mack, NJ, Ahmad, N
Antioxidants & redox signaling. 2018;(8):643-661
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Abstract
SIGNIFICANCE Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen species (ROS) or reactive nitrogen species (RNS), and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and nonhistone targets. Recent studies show that sirtuins modulate the regulation of a variety of cellular processes associated with ARS. SIRT1, SIRT3, and SIRT5 protect the cell from ROS, and SIRT2, SIRT6, and SIRT7 modulate key oxidative stress genes and mechanisms. Interestingly, SIRT4 has been shown to induce ROS production and has antioxidative roles as well. CRITICAL ISSUES A complete understanding of the roles of sirtuins in redox homeostasis of the cell is very important to understand the normal functioning as well as pathological manifestations. In this review, we have provided a critical discussion on the role of sirtuins in the regulation of ARS. We have also discussed mechanistic interactions among different sirtuins. Indeed, a complete understanding of sirtuin biology could be critical at multiple fronts. FUTURE DIRECTIONS Sirtuins are emerging to be important in normal mammalian physiology and in a variety of oxidative stress-mediated pathological situations. Studies are needed to dissect the mechanisms of sirtuins in maintaining redox homeostasis. Efforts are also required to assess the targetability of sirtuins in the management of redox-regulated diseases. Antioxid. Redox Signal. 28, 643-661.
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Evaluation of thyroid nodule characteristics in subclinical hypothyroid patients under a myo-inositol plus selenium treatment.
Nordio, M, Basciani, S
European review for medical and pharmacological sciences. 2018;(7):2153-2159
Abstract
OBJECTIVE The anticancer effect of myo-inositol (MI) is catching researchers' attention worldwide. Thyroid nodules (TNs) have been detected by ultrasound (US) in up to 76% of the general population and, although most of them are benign, thyroid cancer is the most common malignancy of the endocrine system. PATIENTS AND METHODS A retrospective, observational study was conducted in 642 patients with suspected hypothyroidism undergoing US. The analysis was addressed exclusively to patients with subclinical hypothyroidism (SCH) or thyroid-stimulating hormone (TSH) levels borderline associated to TNs classified as class I and II; 1 group (control, no. 16) no treatment was prescribed; the other group (treated, no. 18) underwent treatment with 1 tablet containing MI plus selenium (Se) every day, for six months. Clinical data were collected to evaluate the nodular size, number, and elasticity, as well as TSH levels. RESULTS Final data were analyzed from 34 patients: in 76% of mixed TNs was observed a significant reduction of their size and 56% of them significantly regressed nodule stiffness following oral supplementation with MI plus Se. The mean number of mixed nodules for patient shifted from 1.39 ± 0.16 to 1.05 ± 0.15 (p ≤ 0.05). TSH levels dropped from 4.2 ± 0.21 mIU/L at baseline to 2.1 ± 0.20 mIU/L post-treatment (p < 0.001). In the control group, 38% of TNs reduced their diameter but TSH levels significantly increased up to the threshold after six months (from 3.95 ± 0.18 mIU/L to 4.30 ± 0.22 mIU/L, p ≤ 0.05). CONCLUSIONS In SCH patients undergoing treatment with MI plus Se, a reduction of the size, number and elasticity score of TNs as well as TSH levels was observed. Further studies are required, either in vitro and in vivo, to investigate the use of MI plus Se for the management of TNs.
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The Link Between Selenium, Oxidative Stress and Pregnancy Induced Hypertensive Disorders.
Bizerea, TO, Dezsi, SG, Marginean, O, Stroescu, R, Rogobete, A, Bizerea-Spiridon, O, Ilie, C
Clinical laboratory. 2018;(10):1593-1610
Abstract
BACKGROUND The first line of defence against oxidative stress (OS) are the endogenous antioxidants, such as the Se containing compounds. During pregnancy, OS is caused by the intense growth activity of the fetus; therefore, the placenta is a key place for the activity of many seleno-compounds such as glutathione-peroxidase and thioredoxinreductase. METHODS This review aims to establish the link between the type of selenium compounds, their concentration, their metabolic pathways, and their role in both physiologic and pathologic processes during pregnancy. RESULTS A review of current literature establishes that Se containing compounds have a strong antioxidant effect. The limits that define deviations from the normal concentration range of selenium are very close. Both selenium deficiency and excess have an effect on human health. It is well known that oxidative stress, namely the increase in the concentration of reactive species of oxygen and nitrogen (ROS and RNS) and the disruption of cellular redox homeostasis, are responsible for a number of inflammatory, degenerative, autoimmune, and neoplastic diseases. Selenium deficiency in the pregnant woman's body is considered a risk factor for immune deficiency, PIH, spontaneous abortions, and premature birth. In regard to the fetus, while there seems to be a certain protection against selenium-induced toxicity, studies have shown that selenium defficiency leads to IUGR and SGA newborns. Also, combined deficiency of selenium and iodine has been linked to endemic cretinism in newborns. CONCLUSIONS The antioxidant role that selenium performs through selenoproteins is major. Selenium-containing proteins, especially glutathione peroxidase, as antioxidant enzymes, are involved in regulating the ROS and RNS levels and redox balancing in almost all tissues. Among the multiple benefits of selenium in optimal concentrations in the body are stimulation and support of female fertility, as well as good development of the fetus. Hypertensive pathologies that occur in one of ten pregnant women, especially during the second part of the gestation period, are largely due to selenium deficiency.
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Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders.
Mousavinejad, E, Ghaffari, MA, Riahi, F, Hajmohammadi, M, Tiznobeyk, Z, Mousavinejad, M
Psychiatry research. 2018;:62-69
Abstract
Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ10, MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ10 at daily doses of 30 and 60 mg. Data on children's behavior were collected from parents and babysitters. CoQ10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. A relation was seen between serum MDA (r2 = 0.668) and TAS (r2 = 0.007), and antioxidant enzymes (SOD [r2 = 0.01] and GPx [r2 = 0.001]) activity and CARS score. Based on the results, high doses of CoQ10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs with an increase in the CoQ10 of the serum. We concluded that the serum concentration of CoQ10 and oxidative stress could be used as relevant biomarkers in helping the improvement of ASDs.
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Dietary soybean isoflavones in Alzheimer's disease prevention.
Lu, Y, An, Y, Lv, C, Ma, W, Xi, Y, Xiao, R
Asia Pacific journal of clinical nutrition. 2018;(5):946-954
Abstract
Soybean isoflavone (SIF) is a type of polyphenol present extensively in legumes. Because of its unique chemical construction and the physiological activity of the phenolic hydroxyl group, SIF exhibits strong antioxidant activity in antioxidant and nonantioxidant enzyme systems. Genistein is the major isoflavone in soy foods, accounting for more than 50% of the isoflavone content. The health effects of soybean dietary isoflavones on humans have gained increased attention. Recent studies have suggested that SIF may alleviate neurodegenerative diseases such as Alzheimer's disease (AD). Despite the comprehensive research on AD, effective treatments for AD are yet to be established. The early diagnosis and prevention of mild cognitive impairment (MCI) have become crucial for delaying AD development. Several dietary polyphenols have exerted cognitive effects on AD, and the appropriate intake of dietary SIF helps reduce the risk of AD. This study reviews the possible mechanisms of AD pathogenesis and their relationships with SIF intake; the results provide useful insights for AD prevention in the future.
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Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil.
Quintero-Flórez, A, Pereira-Caro, G, Sánchez-Quezada, C, Moreno-Rojas, JM, Gaforio, JJ, Jimenez, A, Beltrán, G
European journal of nutrition. 2018;(5):1925-1946
Abstract
AIM: This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability. METHODS 'Picual', 'Blanqueta', 'Sevillana', 'Habichuelero', and 'Chetoui' olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells. RESULTS Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. 'Sevillana' VOO had the highest total bioaccessibility (36%), followed by the 'Picual' (19%), 'Chetoui' (17%), 'Habichuelero' (10%), and 'Blanqueta' (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, 'Chetoui', and 'Blanqueta'-BF having the highest radical DPPH scavenging capacity, and 'Habichuelero' and 'Picual'-BF showing protective effects against the peroxyl radical measured by ORACFL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells. CONCLUSIONS Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.
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Phytochemical Profile and Biological Activities of Satureja hortensis L.: A Review of the Last Decade.
Fierascu, I, Dinu-Pirvu, CE, Fierascu, RC, Velescu, BS, Anuta, V, Ortan, A, Jinga, V
Molecules (Basel, Switzerland). 2018;(10)
Abstract
Satureja hortensis L. (summer savory) is an annual herbaceous crop, native to Europe and in our days spread and used all over the world. Although its use as spice and medicinal plant is known since ancient times, peer-reviewed studies presenting the scientific data are scarce. The natural products obtained from summer savory (extracts and essential oil) are dominated by polyphenols and flavonoids, responsible for their antioxidant, antimicrobial, antiparasitic, pesticidal, anti-inflammatory, analgesic, hepatoprotective and anticancer properties, among others. The current study presents the progress made in the last decade regarding the potential applications of summer savory, being the first review study focused on S. hortensis, in the same time suggesting future research opportunities, as they appear from the properties of other Satureja species. The available data presenting the properties of summer savory represents a scientific support for application in industry, for developing "clean label" food products.
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Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease.
Calzetta, L, Matera, MG, Rogliani, P, Cazzola, M
Expert review of respiratory medicine. 2018;(8):693-708
Abstract
N-acetyl-l-cysteine (NAC), a derivative of the naturally occurring amino acid l-cysteine, is a mucolytic agent that may also act as an antioxidant by providing cysteine intracellularly for increased production of glutathione. It is also used for the treatment of acetaminophen overdose. Areas covered: The recent international recommendations for the treatment of chronic obstructive pulmonary disease (COPD) report that NAC, because of its mucolytic activity, reduces acute exacerbation of COPD (AECOPD) with a modest improvement in health status. However, NAC is a pleiotropic drug with heterogeneous pharmacologic characteristics that certainly include mucolytic activity, but also has anti-infective properties and specific antioxidant and anti-inflammatory effects in the airways. Thus, the mechanisms leading to the protective role of this agent against AECOPD need to be adequately addressed. Expert commentary: The protective effect of NAC against AECOPD seems to be related not only to its well-documented mucolytic activity but also to activation of antioxidant pathways, inhibition of pro-oxidant and inflammatory pathways, and modulation of human bronchial tone. Thus, the dogma that NAC acts prevalently as a mucolytic agent is outdated, and the hypothesis that its anti-inflammatory effect is secondary to the antioxidant activity has been rejected.
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Polyunsaturated fatty acids supplementation impairs anti-oxidant high-density lipoprotein function in heart failure.
Wurm, R, Schrutka, L, Hammer, A, Moertl, D, Berger, R, Pavo, N, Lang, IM, Goliasch, G, Huelsmann, M, Distelmaier, K
European journal of clinical investigation. 2018;(9):e12998
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Abstract
BACKGROUND The underlying reasons for the highly inconsistent clinical outcome data for omega-3-polyunsaturated fatty acids (n3-PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, double-blind, placebo controlled study was to determine the effects of oral treatment with n3-PUFAs on the anti-oxidant capacity of HDL in heart failure (HF) patients. METHODS A total of 40 patients with advanced HF of nonischaemic origin, defined by NT-proBNP levels of >2000 pg/mL, NYHA class III or IV and a LVEF <35% who were on stable optimized medical therapy for ≥3 months, were consecutively enrolled into this prospective, double-blind, placebo-controlled trial and randomized in a 1:1:1 fashion to receive 1 g/day or 4 g/day of n3-PUFA, or placebo, respectively, for 12 weeks. RESULTS After 12 weeks of treatment, the anti-oxidant function of HDL, measured by the HDL inflammatory index, was found significantly impaired in the treatment group in a dose-dependent fashion with 0.67 [IQR 0.49-1.04] for placebo vs 0.71 [IQR 0.55-1.01] for 1 g/day n3-PUFA vs 0.98 [IQR 0.73-1.16] for 4 g/day n3-PUFA (P for trend = 0.018). CONCLUSION We provide evidence for an adverse effect of n3-PUFA supplementation on anti-oxidant function of HDL in nonischaemic heart failure patients, establishing a potential mechanistic link for the controversial outcome data on n3-PUFA supplementation.
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Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials.
Namazi, N, Larijani, B, Azadbakht, L
Clinical nutrition (Edinburgh, Scotland). 2018;(2):419-428
Abstract
BACKGROUND & AIMS Previous studies have supported positive roles of antioxidant supplements on weight-loss. One antioxidant supplement is Alpha-lipoic acid. However, recommending ALA as an anti-obesity supplement remains controversial. Accordingly, the purpose of the present study was to perform a meta-analysis on the effects of ALA supplement on anthropometric indices among adult subjects. METHODS We searched five electronic databases till September 2016. Placebo-controlled clinical trials were included. Weighted Mean Difference (WMD) was pooled using a random-effects model. RESULTS Findings of 12 included trials indicated that ALA supplement reduced body weight (WMD: -0.69 kg; 95% CI: -1.27, -0.10; I2 = 0%) and BMI (WMD: -0.38 kg/m2; 95% CI: -0.53, -0.24; I2 = 0%) significantly compared to the placebo group. However, its effects on Waist Circumference (WC) was not significant (WMD: -0.30 cm; 95% CI: -1.18, 0.58; I2 = 17.8%). Stratification by health status indicated that ALA decreased WC in unhealthy subjects (WMD: -2.00 cm; 95% CI: -4.19, 0.19; I2 = 1.3%) more than healthy individuals (0.03 cm; 95% CI: -0.69, 0.75; I2 = 0%). CONCLUSIONS The present study revealed that supplementation with ALA slightly but significantly decreased body weight and BMI. Safe dosage for ALA is up to 1200 mg/day. However, it seems that ALA cannot be cost-effective. Further studies are needed to clarify the effects of ALA on metabolic parameter in unhealthy obese individuals.