-
1.
Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial.
Lashch, NU, Kamchatnov, PR, Fedorova, TN, Muzychuk, OA, Khacheva, KK, Pizova, NV, Malygin, AU, Shavlovskaya, OA, Fateeva, VV, Nikulina, KV, et al
Cerebrovascular diseases (Basel, Switzerland). 2021;(4):472-482
Abstract
OBJECTIVE The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. STUDY DESIGN The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. SETTING The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. INTERVENTIONS Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. OUTCOMES The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. RESULTS 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (n = 65) or a placebo (n = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, p = 0.0272 [p = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (p = 0.007 [p = 0.0107]). CONCLUSIONS Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.
-
2.
Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial.
Safe, IP, Amaral, EP, Araújo-Pereira, M, Lacerda, MVG, Printes, VS, Souza, AB, Beraldi-Magalhães, F, Monteiro, WM, Sampaio, VS, Barreto-Duarte, B, et al
Frontiers in immunology. 2020;:602589
Abstract
Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.
-
3.
N-Acetyl-Cysteine Supplementation Improves Functional Connectivity Within the Cingulate Cortex in Early Psychosis: A Pilot Study.
Mullier, E, Roine, T, Griffa, A, Xin, L, Baumann, PS, Klauser, P, Cleusix, M, Jenni, R, Alemàn-Gómez, Y, Gruetter, R, et al
The international journal of neuropsychopharmacology. 2019;(8):478-487
Abstract
BACKGROUND There is increasing evidence that redox dysregulation, which can lead to oxidative stress and eventually to impairment of oligodendrocytes and parvalbumin interneurons, may underlie brain connectivity alterations in schizophrenia. Accordingly, we previously reported that levels of brain antioxidant glutathione in the medial prefrontal cortex were positively correlated with increased functional connectivity along the cingulum bundle in healthy controls but not in early psychosis patients. In a recent randomized controlled trial, we observed that 6-month supplementation with a glutathione precursor, N-acetyl-cysteine, increased brain glutathione levels and improved symptomatic expression and processing speed. METHODS We investigated the effect of N-acetyl-cysteine supplementation on the functional connectivity between regions of the cingulate cortex, which have been linked to positive symptoms and processing speed decline. In this pilot study, we compared structural connectivity and resting-state functional connectivity between early psychosis patients treated with 6-month N-acetyl-cysteine (n = 9) or placebo (n = 11) supplementation with sex- and age-matched healthy control subjects (n = 74). RESULTS We observed that 6-month N-acetyl-cysteine supplementation increases functional connectivity along the cingulum and more precisely between the caudal anterior part and the isthmus of the cingulate cortex. These functional changes can be partially explained by an increase of centrality of these regions in the functional brain network. CONCLUSIONS N-acetyl-cysteine supplementation has a positive effect on functional connectivity within the cingulate cortex in early psychosis patients. To our knowledge, this is the first study suggesting that increased brain glutathione levels via N-acetyl-cysteine supplementation may improve brain functional connectivity.
-
4.
A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels.
Lindschinger, M, Tatzber, F, Schimetta, W, Schmid, I, Lindschinger, B, Cvirn, G, Stanger, O, Lamont, E, Wonisch, W
Oxidative medicine and cellular longevity. 2019;:6082613
Abstract
The vitamin B complex comprises 8 different water-soluble constituents that humans must sequester from the diet. This pilot study compared natural versus synthetic vitamin B complexes for their bioavailability, accumulation, and their impact on antioxidants, homocysteine levels, and oxidative stress. We conducted a double-blind randomized clinical trial with thirty healthy participants. They were randomly assigned to group N (natural) and group S (synthetic). Vitamin B was ingested daily for 6 weeks in the range of about 2.5 times above the recommended daily allowance. Blood samples were taken at baseline, 1.5 h, 4 h, 7 h (diurnal), 6 w (discontinuation of supplements), and 8 w (washout). Blood levels of thiamine (B1), riboflavin (B2), pyridoxine (B6), folic acid (B9), cobalamin (B12), homocysteine, total antioxidants, peroxidase activity, polyphenols, and total peroxides were determined. Compared to initial values, serum levels of each B vitamin increased at the end of the supplementation period: i.e., B1 (+23% N; +27% S), B2 (+14% N; +13% S), B6 (+101% N; +101% S), B9 (+86% N; +153% S), and B12 (+16% N) (p < 0.05). Homocysteine (-13% N) decreased, while peroxidase activity (+41% S) and antioxidant capacity increased (+26% N). Short-term effects were already observed after 1.5 h for B9 (+238% N; +246% S) and after 4 h for vitamin B2 (+7% N; +8% S), B6 (+59% N; +51% S), and peroxidase activity (+58% N; +58% S). During the washout period, serum levels of B vitamins decreased except for thiamine and peroxidase activity, which increased further. This clinical pilot study revealed comparable bioavailability for both natural and synthetic B vitamins but did not show statistically noticeable differences between groups despite some favourable tendencies within the natural vitamin group, i.e., sustained effects for cobalamin and endogenous peroxidase activity and a decrease in homocysteine and oxidative stress levels.
-
5.
Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity.
Schwartz, JR, Henry, JP, Kerr, KM, Flagler, MJ, Page, SH, Redman-Furey, N
Journal of cosmetic dermatology. 2018;(1):105-111
Abstract
OBJECTIVES To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function. METHODS A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption). CONCLUSIONS Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.
-
6.
The effects of polyunsaturated fatty acids and antioxidant vitamins on atrial oxidative stress, nitrotyrosine residues, and connexins following extracorporeal circulation in patients undergoing cardiac surgery.
Petersen, F, Rodrigo, R, Richter, M, Kostin, S
Molecular and cellular biochemistry. 2017;(1-2):27-40
Abstract
Cardiac surgery with extracorporeal circulation is characterized by different degrees of myocardial ischemia/reperfusion, which is often associated with postoperative atrial fibrillation (POAF). We have previously shown that a novel preventive therapy based on the reinforcement of the antioxidant system using omega-3 fatty acids plus antioxidant vitamin supplementation applied to patients undergoing cardiac surgery reduces POAF occurrence. We hypothesized that oxidative stress and nitrosative stress are involved in the development of an arrhythmogenic substrate by their effect on connexins (Cx40, Cx43 and Cx45) abundance and distribution pattern. Therefore, we have assessed the effect of redox status on atrial tissue in patients undergoing cardiac surgery. Placebo/POAF and supplemented/POAF patients showed 276 and 170% higher reactive oxygen species (ROS) levels and 223 and 96% higher nitrotyrosine residues levels, respectively, compared to sinus rhythm (SR). In POAF tissue, antioxidant supplementation prevented Cx40 and Cx43 lateralization on cardiomyocyte sarcolemma, keeping them at the intercalated disks. POAF samples showed Cx40 heterogeneous distribution pattern, presenting tissue areas lacking this protein (49 and 55% lower levels in placebo/POAF and supplemented/POAF groups, respectively, compared to SR). Of note, Cx45 overexpression occurred in POAF, being 211 and 167% higher in placebo/POAF and supplemented/POAF groups, respectively, compared to SR. It is concluded that treatment with omega-3 fatty acids and antioxidant vitamins reduces oxidative and nitrosative stress and prevents Cx40/Cx43 lateralization in atrial tissue likely contributing to POAF prevention. However, it failed to fully prevent POAF occurrence because these compounds have no effects on the normalization of Cx40 down-regulation and Cx45 up-regulation, which may promote POAF.
-
7.
Effect of Cruciferous Vegetable Intake on Oxidative Stress Biomarkers: Differences by Breast Cancer Status.
Wirth, MD, Murphy, EA, Hurley, TG, Hébert, JR
Cancer investigation. 2017;(4):277-287
-
-
Free full text
-
Abstract
This post hoc analysis examined cruciferous vegetable intake on urinary oxidative metabolites in postmenopausal women. Intervention participants (n = 69) received cruciferous vegetables (≥14 cups/week) during a 3-week period. First morning urine measured 8-isoprostane and 8-hydroxy-2'-deoxyguanosine. Dietary intake was estimated using 24-h recalls. When stratified by history of breast cancer, those with breast cancer had significantly lower post-intervention urinary 8-hydroxy-2'-deoxyguanosine values in the intervention arm versus. the control arm (1.1 ng/mL vs. 3.2 ng/mL, p = .01) after adjustment for baseline 8-hydroxy-2'-deoxyguanosine. This was not observed in those without breast cancer. Further work is needed to understand the role of breast cancer in these relationships.
-
8.
Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study.
Liu, CK, Lyass, A, Larson, MG, Massaro, JM, Wang, N, D'Agostino, RB, Benjamin, EJ, Murabito, JM
Age (Dordrecht, Netherlands). 2016;(1):1
Abstract
Cardiovascular disease and frailty frequently occur together. Both are associated with inflammation, which may be partially triggered by oxidative stress, especially in cardiovascular disease. We investigated whether inflammatory and oxidative stress biomarkers linked to cardiovascular disease were associated with frailty and the related outcome of gait speed. We report cross-sectional associations of biomarkers and frailty assessed at Framingham Offspring Study cycle eight. Participants ≥60 years were eligible if they had information on frailty and at least one of the following: C-reactive protein, interleukin-6, tumor necrosis factor receptor 2, 8-epi-FGFα isoprostanes (isoprostanes), lipoprotein phospholipase A2 (LpPLA2) mass or activity, osteoprotegerin, intracellular adhesion molecule-1, monocyte chemoattractant protein-1 or P-selectin. Stepwise logistic models were utilized for frailty and stepwise linear models for gait speed. Covariates included age, sex, body mass index, smoking, and co-morbidities. Odds ratios (ORs) and slope estimates (B) are reported per standard deviation increase of loge-transformed biomarker. Of the 1919 participants, 142 (7 %) were frail. In a stepwise model, frailty odds increased with higher interleukin-6 (OR 1.90, 95 % CI 1.51, 2.38), isoprostanes (OR 1.46, 95 % CI 1.12, 1.92), and LpPLA2 mass (OR 1.29, 95 % CI 1.00, 1.65). Stepwise regression found that slower gait speeds were associated with interleukin-6 (B = -0.025 m/s, 95 % CI 0.04, -0.01), isoprostanes (B = -0.019, 95 % CI -0.03, -0.008), LpPLA2 mass (B = -0.016, 95 % CI -0.03, -0.004), and osteoprotegerin (B = -0.015, 95 % CI -0.03, -0.002, all p < 0.05). Interleukin-6, isoprostanes, and LpPLA2 mass were associated with greater frailty odds and slower gait speeds. Oxidative stress may be a mechanism contributing to frailty.
-
9.
Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress.
Yeung, CK, Billings, FT, Claessens, AJ, Roshanravan, B, Linke, L, Sundell, MB, Ahmad, S, Shao, B, Shen, DD, Ikizler, TA, et al
BMC nephrology. 2015;:183
Abstract
BACKGROUND Coenzyme Q10 (CoQ10) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity in patients with congestive heart failure. There are no studies evaluating the safety, tolerability and efficacy of varying doses of CoQ10 in chronic hemodialysis patients, a population subject to increased oxidative stress. METHODS We performed a dose escalation study to test the hypothesis that CoQ10 therapy is safe, well-tolerated, and improves biomarkers of oxidative stress in patients receiving hemodialysis therapy. Plasma concentrations of F2-isoprostanes and isofurans were measured to assess systemic oxidative stress and plasma CoQ10 concentrations were measured to determine dose, concentration and response relationships. RESULTS Fifteen of the 20 subjects completed the entire dose escalation sequence. Mean CoQ10 levels increased in a linear fashion from 704 ± 286 ng/mL at baseline to 4033 ± 1637 ng/mL, and plasma isofuran concentrations decreased from 141 ± 67.5 pg/mL at baseline to 72.2 ± 37.5 pg/mL at the completion of the study (P = 0.003 vs. baseline and P < 0.001 for the effect of dose escalation on isofurans). Plasma F2-isoprostane concentrations did not change during the study. CONCLUSIONS CoQ10 supplementation at doses as high as 1800 mg per day was safe in all subjects and well-tolerated in most. Short-term daily CoQ10 supplementation decreased plasma isofuran concentrations in a dose dependent manner. CoQ10 supplementation may improve mitochondrial function and decrease oxidative stress in patients receiving hemodialysis. TRIAL REGISTRATION This clinical trial was registered on clinicaltrials.gov [NCT00908297] on May 21, 2009.
-
10.
Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.
Conrad, C, Lymp, J, Thompson, V, Dunn, C, Davies, Z, Chatfield, B, Nichols, D, Clancy, J, Vender, R, Egan, ME, et al
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2015;(2):219-27
Abstract
PURPOSE To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.