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Differentially expressed plasma proteins of β-thalassemia/hemoglobin E patients in response to curcuminoids/vitamin E antioxidant cocktails.
Panachan, J, Chokchaichamnankit, D, Weeraphan, C, Srisomsap, C, Masaratana, P, Hatairaktham, S, Panichkul, N, Svasti, J, Kalpravidh, RW
Hematology (Amsterdam, Netherlands). 2019;(1):300-307
Abstract
OBJECTIVE Iron overload and oxidative stress are the major causes of serious complications and mortality in thalassemic patients. Our previous work supports the synergistic effects of antioxidant cocktails (curcuminoids or vitamin E, N-acetylcysteine, and deferiprone) in treatment of β-thalassemia/Hb E patients. This further 2-DE-based proteomic study aimed to identify the plasma proteins that expressed differentially in response to antioxidant cocktails. METHODS Frozen plasma samples of ten normal subjects and ten β-thalassemia/Hb E patients at three-time points (baseline, month 6, and month 12) were reduced the dynamic range of proteome using ProteoMiner kit and separated proteins by two-dimensional gel electrophoresis. Differentially expressed proteins were identified using tandem mass spectrometry. Several plasma proteins were validated by ELISA and Western blot analysis. RESULTS Thirteen and 11 proteins were identified with altered expression levels in the curcuminoids- and vitamin E cocktail groups, respectively. The associations between vitronectin (VTN) expression and total bilirubin levels, as well as between serum paraoxonase/arylesterase 1 (PON1) expression and blood reactive oxygen species were observed. Validation results were consistent with proteomics results. DISCUSSION AND CONCLUSIONS These plasma proteins may provide better understanding of the mechanisms underlying the therapeutic effects of antioxidant cocktails in thalassemic patients.
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N-acetylcysteine as a single therapy for sudden deafness.
Chen, CH, Young, YH
Acta oto-laryngologica. 2017;(1):58-62
Abstract
CONCLUSION Like NAC ameliorates hearing loss from acoustic trauma in the inner ear, NAC may also rescue hearing loss from sudden deafness confined to the inner ear. OBJECTIVE This study assesses the effect of N-acetyl-L-cysteine (NAC) as a single therapy for sudden deafness. METHODS Thirty-five sudden deafness patients with neither systemic disorders nor central signs in electronystagmography were treated with NAC alone and assigned to Group A. For comparison, another 35 sudden deafness patients treated by corticosteroids and plasma expander were assigned to Group B. There were no significant differences between the two groups in terms of age, sex, laterality, and pre-treatment mean hearing level. All patients underwent an inner ear test battery comprising audiometry, and ocular vestibular-evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests. RESULTS Groups A and B did not significantly differ in the pre-treatment mean hearing level, and percentages of abnormal oVEMP, cVEMP, and caloric tests, indicating that the involvement severity of sudden deafness between the two groups was similar. However, Group A (43 ± 27 dB) showed significantly greater mean hearing gain than Group B (21 ± 28 dB), and Group A (91%) revealed better improved rate of hearing than Group B (57%).
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Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.
Nagase, M, Yamamoto, Y, Miyazaki, Y, Yoshino, H
Redox report : communications in free radical research. 2016;(3):104-12
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Abstract
OBJECTIVES AND METHODS Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. RESULTS AND DISCUSSION Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.
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Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: a metabolomics overview.
Pallotta, V, Gevi, F, D'alessandro, A, Zolla, L
Blood transfusion = Trasfusione del sangue. 2014;(3):376-87
Abstract
BACKGROUND Recent advances in red blood cell metabolomics have paved the way for further improvements of storage solutions. MATERIALS AND METHODS In the present study, we exploited a validated high performance liquid chromatography-mass spectrometry analytical workflow to determine the effects of vitamin C and N-acetylcysteine supplementation (anti-oxidants) on the metabolome of erythrocytes stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol medium under blood bank conditions. RESULTS We observed decreased energy metabolism fluxes (glycolysis and pentose phosphate pathway). A tentative explanation of this phenomenon could be related to the observed depression of the uptake of glucose, since glucose and ascorbate are known to compete for the same transporter. Anti-oxidant supplementation was effective in modulating the redox poise, through the promotion of glutathione homeostasis, which resulted in decreased haemolysis and less accumulation of malondialdehyde and oxidation by-products (including oxidized glutathione and prostaglandins). DISCUSSION Anti-oxidants improved storage quality by coping with oxidative stress at the expense of glycolytic metabolism, although reservoirs of high energy phosphate compounds were preserved by reduced cyclic AMP-mediated release of ATP.
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Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy.
Riga, MG, Chelis, L, Kakolyris, S, Papadopoulos, S, Stathakidou, S, Chamalidou, E, Xenidis, N, Amarantidis, K, Dimopoulos, P, Danielides, V
American journal of clinical oncology. 2013;(1):1-6
Abstract
OBJECTIVES Ototoxicity is a common and irreversible adverse effect of cisplatin treatment with great impact on the patients' quality of life. N-acetylcysteine is a low-molecular-weight agent which has shown substantial otoprotective activity. The role of transtympanic infusions of N-acetylcysteine was examined in a cohort of patients treated with cisplatin-based regimens. PATIENTS AND METHODS Twenty cisplatin-treated patients were subjected, under local anesthesia, to transtympanic N-acetylcysteine (10%) infusions in 1 ear, during the hydration procedure preceding intravenous effusion of cisplatin. The contralateral ear was used as control. The number of transtympanic infusions was respective to the number of administered cycles. Hearing acuity was evaluated before each cycle with pure tone audiometry by an audiologist blinded to the treated ear. RESULTS A total of 84 transtympanic infusions were performed. In treated ears, no significant changes in auditory thresholds were recorded. In the control ears cisplatin induced a significant decrease of auditory thresholds at the 8000 Hz frequency band (P=0.008). At the same frequency (8000 Hz), the changes in auditory thresholds were significantly larger for the control ears than the treated ones (P=0.005). An acute pain starting shortly after the injection and lasting for a few minutes seemed to be the only significant adverse effect. CONCLUSIONS Transtympanic injections of N-acetylcysteine seem to be a feasible and effective otoprotective strategy for the prevention of cisplatin-induced ototoxicity. Additional studies are required to further clarify the efficiency of this treatment and determine the optimal dosage and protocol.
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Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.
Carmeli, C, Knyazeva, MG, Cuénod, M, Do, KQ
PloS one. 2012;(2):e29341
Abstract
UNLABELLED Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION ClinicalTrials.gov NCT01506765.
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Effect of hydration with or without n-acetylcysteine on contrast induced nephropathy in patients undergoing coronary angiography and percutaneous coronary intervention.
Awal, A, Ahsan, SA, Siddique, MA, Banerjee, S, Hasan, MI, Zaman, SM, Arzu, J, Subedi, B
Mymensingh medical journal : MMJ. 2011;(2):264-9
Abstract
Contrast induced nephropathy (CIN), an acute decline in renal function after the administration of intravenous contrast in the absence of other causes, is the third leading cause of acute renal failure in hospitalized patients. Antioxidant N-acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who underwent coronary angiography (CAG) and percutaneous coronary intervention (PCI). Hydration is the cornerstone in preventing CIN. N-acetylcysteine has additive preventive affect. We compared N-acetylcysteine plus hydration with hydration alone in preventing CIN. Patients were assigned to receive either premedication with hydration with normal saline (1ml/kg/hour-12 hour before and 12 hour after CAG and intravenous PCI) alone or to receive both hydration and oral N acetylcysteine (600mg bid for 2 days, starting day before CAG and PCI). Main out come was occurrence of ≥25% or ≥0.5mg/dl increase in serum creatinine level within 24 to 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. Six patients (12%) of hydration group i.e. Group A and none of the patients of N-acetylcysteine All group i.e. Group B develop CIN (p=0.012). Baseline serum creatinine level was slightly higher in N-acetylcysteine group than hydration group (1.52±0.32 and 1.44±0.22). After 24 hours of CAG and PCI serum creatinine level lower than base line in N-acetylcysteine group but slightly higher than base line in hydration group (1.42±0.39 and 1.51±0.38). Difference in serum creatinine in both the groups were statistically significant (p=0.006 in N-acetylcysteine group and p=0.029 in hydration group). Creatinine clearance rate significantly improved in N-acetylcysteine group after coronary intervention. In conclusion, N-acetylcysteine and hydration prevent CIN better than hydration alone in high risk patients.
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Proanthocyanidins in buckwheat flour can reduce salivary nitrite to nitric oxide in the stomach.
Takahama, U, Tanaka, M, Hirota, S
Plant foods for human nutrition (Dordrecht, Netherlands). 2010;(1):1-7
Abstract
Buckwheat flour, which is used for various dishes in the world, is a good source of proanthocyanidins. Proanthocyanidins in the buckwheat flour reduced nitrous acid producing nitric oxide (NO) when the flour was suspended in acidified saliva or in acidic buffer solution in the presence of nitrite. The ingestion of dough prepared from buckwheat flour increased the concentration of NO in the air expelled from the stomach, suggesting that the proanthocyanidins also reduced nitrite to NO in the stomach. During the production of NO by the buckwheat flour/nitrous acid systems, oxidation, nitration, and nitrosation of proanthocyanidins proceeded. The increase in the concentration of NO could improve the activity of stomach helping the digestion of ingested foods and the nitration and nitrosation of the proanthocyanidins could contribute to the scavenging of reactive nitrogen oxide species generated from NO and nitrous acid.
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N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis.
Rosato, E, Cianci, R, Barbano, B, Menghi, G, Gigante, A, Rossi, C, Zardi, EM, Amoroso, A, Pisarri, S, Salsano, F
Acta pharmacologica Sinica. 2009;(9):1283-8
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Abstract
AIM: To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. METHODS In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g x kg(-1) x h(-1). Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. RESULTS NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. CONCLUSION In patients with low disease severity NAC ameliorates vascular renal function.
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Effects of N-acetylcysteine on respiratory muscle fatigue during heavy exercise.
Kelly, MK, Wicker, RJ, Barstow, TJ, Harms, CA
Respiratory physiology & neurobiology. 2009;(1):67-72
Abstract
Respiratory muscle fatigue (RMF) occurs during heavy exercise in humans. N-acetylcysteine (NAC) infusion has been shown to reduce RMF, suggesting that oxidative stress is a contributing factor. The purpose of the present study was to determine the effect of an acute oral dose of NAC on RMF during heavy exercise. Subjects (n=8) were given either placebo (PLA) or NAC (1,800 mg) 45 min prior to a 30 min constant load (85V(O)(2peak)), discontinuous exercise test. Maximum respiratory pressures (inspiratory, PI(max); expiratory, PE(max)) and venous blood samples were made prior to and following each 5 min of exercise. There was no difference (p>0.05) in PI(max) between NAC (127.9+/-34.1 cm H(2)O) or PLA (134.1+/-28.1cm H(2)O) at rest. During exercise, PI(max) was significantly lower with PLA ( approximately 14%) compared to NAC at 25 and 30 min suggesting less RMF with NAC. There were no differences (p>0.05) between groups in PE(max), V(O)(2), V(E), or heart rate at rest or throughout exercise. These results suggest that an acute dose of NAC reduces RMF during heavy exercise.