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1.
Effect of N-acetylcysteine against Vancomycin-Induced Nephrotoxicity: A Randomized Controlled Clinical Trial.
Badri, S, Soltani, R, Sayadi, M, Khorvash, F, Meidani, M, Taheri, S
Archives of Iranian medicine. 2020;(6):397-402
Abstract
BACKGROUND The proposed mechanism of vancomycin-induced nephrotoxicity (VIN) is indirect production of reactive oxygen species in the kidney tissue. This study aimed to investigate the effectiveness of N-acetylcysteine (NAC), an anti-oxidant agent, in the prevention of VIN. METHODS Patients who received vancomycin for any indication were randomly divided to drug (NAC) and control groups. The patients in the drug group received oral NAC 600 mg every 12 hours for 10 days, starting concurrently with vancomycin. Serum creatinine (SCr) levels and blood urea nitrogen (BUN) as well as creatinine clearance (CrCl) and 12-hour urine volume were recorded at baseline, every other day during the study, and 12 hours after the last dose of vancomycin on the 10th day. Furthermore, the cases of acute kidney injury (AKI; ≥ 0.5 mg/dL or at least 50% increase in serum creatinine from baseline) were recorded in the two groups. RESULTS Over the study period, 84 and 95 patients completed the study in drug and control groups, respectively. SCr and CrCl were significantly lower and higher, respectively, at all-time points (except for baseline) in the NAC compared to the control group. Furthermore, although not statistically significant, 12 cases of vancomycin-induced AKI were observed in the control group (12.63%), while 4 cases (4.76%) were reported from drug group (P = 0.066; relative risk [RR] = 0.377, 95% CI: 0.126-1.124). CONCLUSION NAC has the potential for reduction of VIN. However, more studies are necessary to confirm this effect.
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Protective effect of N-acetylcysteine on oxaliplatin-induced neurotoxicity in patients with colorectal and gastric cancers: A randomized, double blind, placebo-controlled, clinical trial.
Bondad, N, Boostani, R, Barri, A, Elyasi, S, Allahyari, A
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2020;(7):1575-1582
Abstract
PURPOSE Neuropathy is one of the most prevalent and dose-limiting side effects of platinum chemotherapeutic agents. N-acetylcysteine is an antioxidant thiol which is able to increase whole blood concentration of glutathione, which may be protective against chemotherapy-induced neuropathy. The aim of this study was to evaluate the effect of N-acetylcysteine on neurotoxicity induced by oxaliplatin in patients with gastric or colorectal cancers. METHODS During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of N-acetylcysteine effervescent tablets was assessed in comparison with placebo, on neuropathy occurrence. Thirty-two patients with colorectal or gastric cancer randomly received N-acetylcysteine (two 600 mg tablets) or placebo tablets 1 h before receiving oxaliplatin in dose in XELOX (oxaliplatin and capecitabine regimen) for eight courses of chemotherapy. Neuropathy severity was assessed after eight courses of chemotherapy based on National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria neuropathy grading scale and also sensory and motor electrophysiological assessment was performed by a neurologist. RESULTS The NCI-CTCAE scale grade of patients in intervention group was significantly lower than placebo group after eight course of oxaliplatin (P = 0.01); however, the sensory electrophysiological assessment result was not significantly different (P = 0.501). No patient in both group had motor electrophysiological changes. CONCLUSION The results of this study showed that N-acetylcysteine could reduce the incidence of the neuropathy induced by oxaliplatin and delay its occurrence in patients with gastric or colorectal cancers.
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Improvement of cognitive function in schizophrenia with N-acetylcysteine: A theoretical review.
Yolland, COB, Phillipou, A, Castle, DJ, Neill, E, Hughes, ME, Galletly, C, Smith, ZM, Francis, PS, Dean, OM, Sarris, J, et al
Nutritional neuroscience. 2020;(2):139-148
Abstract
Objectives: Schizophrenia is a debilitating psychiatric illness associated with positive and negative symptoms as well as significant impairments in cognition. Current antipsychotic medications do not alleviate these cognitive deficits, and more effective therapeutic options are required. Increased oxidative stress and altered antioxidant levels, including glutathione (GSH) have been observed both in individuals with cognitive impairment and in people with schizophrenia. A GSH precursor, the antioxidant N-acetylcysteine (NAC) has been investigated as a novel treatment for the cognitive symptoms of schizophrenia, and recent research suggests that NAC may be a promising adjunctive treatment option. However, the current literature lacks integration as to why NAC may effectively improve cognition in schizophrenia. The present theoretical synthesis aimed to address this gap by examining the processes by which NAC may improve cognitive function in schizophrenia. Methods: The schizophrenia literature was reviewed in three key domains: cognitive impairment, the relationship between oxidative stress and cognition, and the efficacy of NAC as a novel treatment. This led to a theoretical analysis of the neurobiological processes by which NAC may improve cognition in schizophrenia. Results: This theoretical review concluded that improved cognition may result from a combination of factors, including decreased oxidative stress, neuroprotection of cognitive networks and an increase in glutamatergic modulation of the N-methyl-d-aspartate receptor system. Whilst a number of mechanisms by which NAC may improve cognition and symptoms in schizophrenia have been proposed, there is still limited understanding of the specific metabolic pathways involved and how they interrelate and modify specific symptomology. Discussion: Exploration of how NAC treatment may act to improve cognitive function could guide clinical trials by investigation of the specific neurotransmitter systems and processes involved, allowing for targeted neurological outcome measures. Future research would benefit from the investigation of both in vivo cortical GSH concentration and peripheral plasma GSH in a population of individuals with chronic schizophrenia.
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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.
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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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N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials.
Kishi, T, Miyake, N, Okuya, M, Sakuma, K, Iwata, N
Psychopharmacology. 2020;(11):3481-3487
Abstract
RATIONALE It remains unclear whether using N-acetylcysteine as an adjunctive treatment has any benefit for bipolar depression and major depressive disorder. OBJECTIVES A systematic review and random-effect meta-analysis of double-blind, randomized placebo-controlled trials was conducted to explore the clinical question. METHODS Outcomes included improvement in depression scale scores (primary), Young Mania Rating Scale score, Hamilton Anxiety Rating Scale score, Clinical Global Impression-Severity Scale (CGI-S) score, Global Assessment of Functioning Scale score, Social and Occupational Functioning Assessment Scale score, Range of Impaired Functioning Tool score, Streamed Longitudinal Interval Clinical Evaluation for the Longitudinal Interview Follow-Up Evaluation score, quality of life scales scores, and the incidence of all-cause discontinuation and individual adverse events. RESULTS Seven studies (n = 728, 8-24 weeks, mean age = 46.81, % female = 58.45%) were included. N-acetylcysteine did not improve depressive symptoms compared with placebo (N = 7, n = 579, standardized mean difference (SMD) = - 0.12, 95% confidence interval (95% CI) = - 0.38, 0.14, p = 0.38, I2 = 52.74%). The meta-regression analysis detected an association between effect size and publication year (coefficient = 0.06, 95% CI = 0.00, 0.11, p = 0.04, I2 = 27.56%). Although N-acetylcysteine was superior to placebo in CGI-S score (N = 6, n = 563, SMD = - 0.28, 95% CI = - 0.47, - 0.10, p < 0.01, I2 = 14.88%), there was no significant difference in the other efficacy outcomes between the treatment groups. Although N-acetylcysteine was associated with a higher incidence of gastrointestinal adverse events compared with placebo (N = 4, n = 537, risk ratio = 1.79, 95% CI = 1.37, 2.32, p < 0.01, I2 = 0.00%, number needed to treat to harm = 7), there was no significant difference in all-cause discontinuation and other safety outcomes between the treatments. CONCLUSIONS Although N-acetylcysteine decreased CGI-S score, no specific improvements in symptoms were identified.
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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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Randomized controlled trial of N-acetylcysteine therapy for RYR1-related myopathies.
Todd, JJ, Lawal, TA, Witherspoon, JW, Chrismer, IC, Razaqyar, MS, Punjabi, M, Elliott, JS, Tounkara, F, Kuo, A, Shelton, MO, et al
Neurology. 2020;(13):e1434-e1444
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Abstract
OBJECTIVE To investigate the efficacy of N-acetylcysteine (NAC) for decreasing elevated oxidative stress and increasing physical endurance in individuals with ryanodine receptor 1-related myopathies (RYR1-RM). METHODS In this 6-month natural history assessment (n = 37) followed by a randomized, double-blinded, placebo-controlled trial, 33 eligible participants were block-randomized (1:1) to receive NAC (n = 16) or placebo (n = 17), orally for 6 months (adult dose 2,700 mg/d; pediatric dose 30 mg/kg/d). The primary endpoint was urine 15-F2t isoprostane concentration and the clinically meaningful co-primary endpoint was 6-minute walk test (6MWT) distance. RESULTS When compared to the general population, participants had elevated baseline 15-F2t isoprostane concentrations and most had a decreased 6MWT distance (mean ± SD 3.2 ± 1.5 vs 1.1 ± 1.7 ng/mg creatinine and 468 ± 134 vs 600 ± 58 m, respectively, both p < 0.001). 15-F2t isoprostane concentration and 6MWT distance did not change over the 6-month natural history assessment (p = 0.98 and p = 0.61, respectively). NAC treatment did not improve 15-F2t isoprostane concentration (least squares means difference 0.1 [95% confidence interval [CI] -1.4 to 1.6] ng/mg creatinine, p = 0.88) or 6MWT distance (least squares means difference 24 [95% CI -5.5 to 53.4] m, p = 0.11). NAC was safe and well-tolerated at the doses administered in this study. CONCLUSION In ambulatory RYR1-RM-affected individuals, we observed stable disease course, and corroborated preclinical reports of elevated oxidative stress and decreased physical endurance. NAC treatment did not decrease elevated oxidative stress, as measured by 15-F2t isoprostane. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that, for people with RYR1-RM, treatment with oral NAC does not decrease oxidative stress as measured by 15-F2t isoprostane. CLINICALTRIALSGOV IDENTIFIER NCT02362425.
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Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham-Controlled Pilot Study.
Visser, EJ, Drummond, PD, Lee-Visser, JLA
Pain practice : the official journal of World Institute of Pain. 2020;(7):737-747
Abstract
OBJECTIVE To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect. DESIGN Randomized, double-blind, sham-controlled pilot study. SETTING Australian community. SUBJECTS Adults reporting 2 to 8 migraines per month for at least a year. METHODS After a 1-month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below. RESULTS For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use. CONCLUSIONS This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.
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Comparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis.
Song, Y, Wang, H, Huang, H, Zhu, Z
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2020;(3):204-210
Abstract
Our aim is to evaluate the clinical effectiveness and safety by comparing N-acetyl-cysteine (NAC) with metformin administrated by polycystic ovary syndrome (PCOS) patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. 10 studies were considered eligible for inclusion. NAC significantly reduced BMI and total testosterone, there was no significant difference in pregnancy rate, serum LH level, fasting insulin, and LH/FSH ratio. In conclusions, NAC may be considered as an alternative supplement to metformin, but large-scale randomized controlled trials are needed to assess the efficacy and safety of NAC in PCOS patients.