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Evaluation the Effects of Alpha-tocopherol in Comparison with N-acetylcystein for Prevention of Contrast Induced Nephropathy (CIN) in CKD Patients.
Samadi, K, Naghibi, M, Shabestari, M, Sharifipour, F, Khajeh Dalooee, M, Raeesi, V, Moosavi Nik, S, Samadi, M
Iranian journal of kidney diseases. 2020;(1):26-30
Abstract
INTRODUCTION Contrast induced nephropathy (CIN), a well-known complication of using radio contrast media, dramatically increases the likelihood of patient morbidity and mortality following coronary angiography. As there is no specific treatment for CIN, prevention could be the best strategy to address this issue. Since now, the only approved preventing strategy was hydration with normal saline while antioxidant agents as a new yet unapproved remedy for this purpose could be applied .The present study was conducted to examine the effect of alpha tocopherol in CIN prevention. METHODS This prospective controlled trial was carried out on 201 patients with chronic kidney disease (eGFR < 60 cc/min) underwent coronary angiography. We assigned three groups of CKD patients: 72 patients who received prophylaxis administration with isotonic saline (Group A), 66 patients with isotonic saline plus N-acetylcysteine (1200mg twice a day) for 2 days (Group B) and 63 patients who received isotonic saline plus daily alpha tocopherol (600 IU once daily from one day before till 2 days after angiography) for 4 days (Group C). The contrast media in all three groups was nonionic iso-osmolal agent, Visipaque. RESULTS Even though CIN didn't developed in any of the three aforementioned groups but there was statistically significant reduction in eGFR from baseline in all three groups (P < .001). Moreover, We found no statistically significant difference in GFR reduction between three studied groups. CONCLUSION Administration of alpha tocopherol has no additive beneficial effect over isotonic saline in CIN prevention in CKD patients.
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Evaluation of nebulized N-acetyl cysteine in outcome of esophageal atresia with tracheoesophegeal fistula.
Singh, G, Pandey, A, Shandilya, G, Gupta, A, Rawat, JD, Wakhlu, A, Kureel, SN
Journal of pediatric surgery. 2020;(12):2635-2639
Abstract
AIM: To evaluate the role of nebulized N-acetyl cysteine (NAC) in liquefying the airway secretions and improving the outcome of patients of esophageal atresia with tracheoesophageal fistula (EA + TEF). METHODS It was a non-randomized interventional study. Two milliliters of 10% NAC was given in a nebulized form (2:5 dilution, every six hourly) to patients of ET + TEF, along with regular suction of upper esophageal pouch. The group was compared with control, which comprised patients of EA + TEF receiving only saline nebulization. The consistency of the secretions was compared by hand held consistometer in unit of time (seconds) required to cross a predetermined distance along with gravity. RESULTS Sixty patients were assessed. Of these, 30 patients were present in both groups. The study group showed significant (p = 0.01-0.0001) decrease in consistency of secretions from the control group after day 2 of NAC nebulization. Patients' discharge was significantly (p = 0.01) earlier in cases. There was no significant (p = 0.41) difference in mortality between the groups. No specific adverse effects were observed in the study group. CONCLUSION It appears that nebulized NAC decreases the consistency of secretions in EA + TEF patients. It is interesting to note that the group of patients that received NAC was discharged earlier than the control group and had a higher survival rate than the control group. Whether this is directly attributable to the use of NAC is unknown. A prospective double-blinded randomized clinical trial is warranted to confirm these results. LEVEL OF EVIDENCE Level II, prospective comparative study (non-randomized).
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MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose.
Wong, A, Nejad, C, Gantier, M, Choy, KW, Doery, J, Graudins, A
Human & experimental toxicology. 2019;(6):646-654
Abstract
Paracetamol overdose is common and microRNA (miR)-122 expression is increased with liver injury. We aimed to measure miR-122 in the setting of an abbreviated paracetamol overdose treatment regimen. We compared miRNA expression in patients treated for paracetamol poisoning with an abbreviated 12-h intravenous acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) or a 20-h regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) (NACSTOP trial). miR-122 expression is increased (decreased cycle threshold (Ct) values) with paracetamol liver injury. We assessed miR-122 expression in patients receiving the two acetylcysteine regimens and in a separate group with acute liver injury (ALI). We examined 121 blood samples in 38 patients. After 20 h of acetylcysteine, median alanine transaminase (ALT) was 12 U/L (18, 14) versus 16 U/L (11, 21) ( p = 0.17) and median miR-122 Ct was 30.1 (interquartile range (IQR): 28.9, 33.3) versus 31.4 (28.9, 33.9) ( p = 0.7) in the NACSTOP abbreviated and control groups, respectively. Median normalized miR-122 Ct after 20 h of acetylcysteine was 2.2 (IQR 1.9, 6.4), 1.1 (0.7, 2.9), 63.9 (2.5, 168), 123.2 (40.9, 207.8) in the NACSTOP-abbreviated, NACSTOP-control, ALI and hepatotoxicity groups, respectively. There was no significant difference in ALT or miRNA between NACSTOP treatment groups and no signal of increased liver injury from an abbreviated 12-h acetylcysteine regimen. These findings suggest that an abbreviated acetylcysteine regimen in low-risk patients who have overdosed on paracetamol is safe. Further study is required to validate this finding utilizing miRNA as a comparative biomarker.
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Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.
Coles, LD, Tuite, PJ, Öz, G, Mishra, UR, Kartha, RV, Sullivan, KM, Cloyd, JC, Terpstra, M
Journal of clinical pharmacology. 2018;(2):158-167
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Abstract
Parkinson's disease (PD) is associated with oxidative stress and decreased nigral glutathione (GSH), suggesting that therapies that boost GSH may have a disease-modifying effect. Intravenous administration of a high dose of N-acetylcysteine (NAC), a well-known antioxidant and GSH precursor, increases blood and brain GSH in individuals with PD and with Gaucher disease and in healthy controls. To characterize the pharmacokinetics of repeated high oral doses of NAC and their effect on brain and blood oxidative stress measures, we conducted a 4-week open-label prospective study of oral NAC in individuals with PD (n = 5) and in healthy controls (n = 3). Brain GSH was measured in the occipital cortex using 1 H-MRS at 3 and 7 tesla before and after 28 days of 6000 mg NAC/day. Blood was collected prior to dosing and at predetermined collection times before and after the last dose to assess NAC, cysteine, GSH, catalase, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations and the reduced-to-oxidized GSH ratio (GSH/ glutathione disulfide [GSSG]). Symptomatic adverse events were reported by 3 of the 5 subjects with PD. NAC plasma concentration-time profiles were described by a first-order absorption, 1-compartment pharmacokinetic model. Although peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline, indicators of oxidative damage, that is, measures of lipid peroxidation (4-HNE and MDA) were unchanged. There were no significant increases in brain GSH, which may be related to low oral NAC bioavailability and small fractional GSH/GSSG blood responses. Additional studies are needed to further characterize side effects and explore the differential effects of NAC on measures of antioxidant defense and oxidative damage.
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Antioxidants Taken Orally prior to Diagnostic Radiation Exposure Can Prevent DNA Injury.
Velauthapillai, N, Barfett, J, Jaffer, H, Mikulis, D, Murphy, K
Journal of vascular and interventional radiology : JVIR. 2017;(3):406-411
Abstract
PURPOSE To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage. MATERIALS AND METHODS In a single-center prospective controlled trial, antioxidant treatment with 2 g ascorbate, 1.2 g N-acetylcysteine, 600 mg lipoic acid, and 30 mg beta carotene was given to 5 consecutive participants before undergoing clinically indicated technetium-99m methylene diphosphonate (99mTc MDP) bone scans for cancer staging. These participants were compared with 5 participants without antioxidant treatment. DNA damage was visualized in peripheral blood mononuclear cells (PBMCs) before and after bone scans using three-dimensional microscopy and fluorescently labeled gamma-H2AX protein. Wilcoxon rank sum test was used to determine whether there was a statistically significant difference in the radiation received between the control and antioxidant groups, the number of foci/cell before and after bone scan within groups, and foci/cell after bone scan between groups. RESULTS There was a significantly higher number of gamma-H2AX foci/cell after ionization radiation in the control group compared with the antioxidant group (P = .009). There was no statistically significant difference in number of gamma-H2AX foci/cell before or after exposure in the antioxidant group; the number of gamma-H2AX foci/cell was statistically significantly higher (P = .009) in the control group after exposure to 99mTc MDP. CONCLUSIONS In patients undergoing 99mTc MDP bone scans, treatment with oral antioxidants before scanning significantly prevented DNA damage in PBMCs. Antioxidants may provide an effective means to protect patients and health care professionals from radiation-induced DNA damage during imaging studies.
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Comparison of metformin and N-acetyl cysteine, as an adjuvant to clomiphene citrate, in clomiphene-resistant women with polycystic ovary syndrome.
Nemati, M, Nemati, S, Taheri, AM, Heidari, B
Journal of gynecology obstetrics and human reproduction. 2017;(7):579-585
Abstract
OBJECTIVE To evaluate the effects of short- and long-term treatment with metformin and NAC, in an adjuvant to clomiphene citrate (CC), on the improvement of hormonal profile (SHBG, total testosterone, FBS, and fasting insulin) and fertility status in CC-resistant women with PCOS. MATERIALS AND METHODS One hundred and eight CC-resistant PCOS patients participated in the study and received either metformin (1500mg/day) or NAC (1800mg/day) with 100mg/day of CC for 8 and 12 weeks. Mean BMI, hirsutism score, LH/FSH ratio, endometrial thickness, mature follicle number, and serum concentrations of LH, FSH, E2, fasting insulin, total testosterone and FBS were evaluated before and after short- and long-term treatment. Furthermore, ovulation and pregnancy rates in the first and second cycles were also determined in treated patients. RESULTS There was no significant difference in all variables before and 8 weeks after treatment with metformin and NAC. The BMI- and insulin-lowering effects of metformin were significantly higher than NAC after long-term treatment. However, the reducing-effect of NAC on hirsutism score and FBS levels was significantly more than metformin after 12 weeks. Treatment with metformin and NAC significantly increased ovulation and pregnancy rates in CC-resistant PCOS patients. In the first and second cycles, ovulation and pregnancy rates in patients treated with NAC were slightly higher than those received metformin. CONCLUSIONS Compared with metformin, administration of NAC in an adjuvant to CC is recommended for improving of hormonal profile and treatment of anovulatory infertility in hyperinsulinemic patients especially women with PCOS who are CC-resistant.
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Sodium bicarbonate versus sodium chloride and oral N-acetylcysteine for the prevention of contrast-induced nephropathy in advanced chronic kidney disease.
Shavit, L, Korenfeld, R, Lifschitz, M, Butnaru, A, Slotki, I
Journal of interventional cardiology. 2009;(6):556-63
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INTRODUCTION Contrast-induced acute kidney injury (CI-AKI) is one of the leading causes of hospital-acquired acute kidney injury. Multiple clinical studies have proposed several preventive strategies. AIMS To examine the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine (NAC) for preventive hydration after cardiac catheterization. METHODS We conducted a prospective, single-center trial. Patients with chronic kidney disease (CKD) stage III-IV undergoing cardiac catheterization were allocated to receive either an infusion of 0.9% sodium chloride and oral NAC or 154 mEq/L sodium bicarbonate. MAIN Outcome measure CI-AKI, defined as an increase of 25% or 0.3 mg/dL or more in plasma creatinine within 2 days of contrast administration. RESULTS Ninety-three patients were allocated to one of the two groups: 42 patients in the saline plus NAC group and 51 patients in the bicarbonate group. There were no statistically significant differences between the groups in the most important clinical and procedural characteristics. Baseline plasma creatinine levels, estimated glomerular filtration rate, incidence of diabetes mellitus, hypertension, congestive heart failure, and contrast medium volume were similar. Mean plasma creatinine concentration was 1.76 +/- 0.54 mg/dL in the saline and NAC group and 1.9 +/- 1 mg/dL in the bicarbonate group (P = 0.23). The rate of CI-AKI was 9.8% in the bicarbonate group and 8.4% in the saline plus NAC group. No patient required renal replacement therapy. CONCLUSION Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI-AKI in patients with CKD stage III-IV undergoing cardiac catheterization.
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N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss.
Amin, AF, Shaaban, OM, Bediawy, MA
Reproductive biomedicine online. 2008;(5):722-6
Abstract
Pregnancy could be associated with a state of oxidative stress that could initiate and propagate a cascade of changes that may lead to pregnancy wastage. This process of oxidative stress may be suppressed by the antioxidant effect of N-acetyl cysteine (NAC). The current study aimed to evaluate the effect of NAC therapy in patients diagnosed with unexplained recurrent pregnancy loss (RPL). The study was a prospective controlled study performed in the Women's Health Centre, Assiut University, Egypt. A group of 80 patients with history of recurrent unexplained pregnancy loss were treated with NAC 0.6 g + folic acid 500 microg/day and compared with an aged-matched group of 86 patients treated with folic acid 500 microg/day alone. NAC + folic acid compared with folic acid alone caused a significantly increased rate of continuation of a living pregnancy up to and beyond 20 weeks [P < 0.002, relative risk (RR) 2.9, 95% confidence interval (CI) 1.5-5.6]. NAC + folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone (P < 0.047, RR 1.98, 95% CI 1.3-4.0). In conclusion, NAC is a well-tolerated drug that could be a potentially effective treatment in patients with unexplained RPL.
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High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis.
Tirouvanziam, R, Conrad, CK, Bottiglieri, T, Herzenberg, LA, Moss, RB, Herzenberg, LA
Proceedings of the National Academy of Sciences of the United States of America. 2006;(12):4628-33
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Abstract
Neutrophilic airway inflammation is a hallmark of cystic fibrosis (CF). As high oxidant producers, airway neutrophils contribute largely to the systemic redox imbalance seen in CF. In turn, this chronic and profound imbalance can impact circulating neutrophils before their migration into airways. Indeed, in 18 CF patients with stable disease, blood neutrophils were readily deficient in the pivotal antioxidant glutathione (P = 0.003, compared with 9 healthy controls). In a phase 1 study, this deficiency was improved (P = 0.025) by the glutathione prodrug N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). This treatment was safe and markedly decreased sputum elastase activity (P = 0.006), the strongest predictor of CF pulmonary function. Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005), as measured by flow cytometry. Pulmonary function measures were not improved, as expected with short-term treatment. After excluding data from subjects without baseline airway inflammation, positive treatment effects were more pronounced and included decreased sputum IL-8 levels (P = 0.032). Thus, high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF.
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Prophylactic acetylcysteine usage for prevention of contrast nephropathy after coronary angiography.
Gulel, O, Keles, T, Eraslan, H, Aydogdu, S, Diker, E, Ulusoy, V
Journal of cardiovascular pharmacology. 2005;(4):464-7
Abstract
Radiographic contrast agents can cause acute decrease in renal functions. It is thought that anti-oxidant acetylcysteine can prevent contrast nephropathy. Fifty patients planned to undergo elective diagnostic coronary angiography with serum creatinine values above 1.3 mg/dL were included in the study. Acetylcysteine was given orally at a dose of 600 mg twice daily, on the day before and on the day of administration of contrast agent in the acetylcysteine group (n=25). Acetylcysteine was not given to the control group (n=25). Saline (0.9%) was given intravenously at a rate of 1 mL/kg/h for 12 hours before and 12 hours after administration of contrast agent. Contrast nephropathy was detected in 3 of 25 patients (12%) in the acetylcysteine group and 2 of 25 patients (8%) in the control group (P>0.05). Contrast nephropathy was developed in 2 of 4 patients (50%) with baseline serum creatinine concentrations above 2.5 mg/dL, whereas it was developed in only 3 of 46 patients (6.5%) with baseline serum creatinine concentrations below 2.5 mg/dL (P=0.04). It was detected that in patients planned to undergo elective diagnostic coronary angiography with renal dysfunction, oral acetylcysteine and hydration before the procedure was not more effective than hydration alone in the prevention of contrast nephropathy. High baseline serum creatinine values were detected as a risk factor for development of contrast nephropathy.