A Pilot Study to Evaluate the Effects of Oral N-Acetyl Cysteine on Inflammatory and Oxidative Stress Biomarkers in Rheumatoid Arthritis

Hashemi, Ghazal; Mirjalili, Mahtabalsadat; Basiri, Zahra; Tahamoli-Roudsari, Ahmad; Kheiripour, Nejat; Shahdoust, Maryam; Ranjbar, Akram; Mehrpooya, Maryam; Ataei, Sara

doi:10.2174/1573403x14666180926100811

Cited by 29 publications

(38 citation statements)

References 37 publications

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“…Also, in our previous clinical trial, we found that supplementation with NAC as adjuvant therapy to a standard medication significantly improved pain symptoms in patients suffering from rheumatoid arthritis (RA) 59. Ameliorative effects of NAC on inflammatory and oxidative stress biomarkers may be the mechanism responsible for its beneficial effects on pain symptoms in RA patients 60. In accordance to these studies, the present study also provided further evidence that NAC can be efficacious in improving neuropathic pain associated with diabetic neuropathy, at least in part via ameliorative effects on oxidative stress.…”

Section: Discussionmentioning

confidence: 93%

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy

Heidari¹,

Sajedi²,

Mohammadi³

et al. 2019

JPR

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PurposePainful diabetic neuropathy (PDN) is a variant of diabetic peripheral neuropathy which is highly prevalent and distressing in diabetic patients. Despite its high burden, the optimal treatment of PDN has remained a clinical challenge. To explain the emergence and maintenance of PDN, increasing attention has been focused on dimensions of inflammation and oxidative toxic stress (OTS). Accordingly, the aim of this study was to investigate the effects of oral N-acetylcysteine (NAC), an agent with known anti-oxidant and anti-inflammatory effects, as an adjunct therapy in patients suffering from PDN.Patients and methods113 eligible patients with type 2 diabetes suffering from PDN were randomly assigned to either the pregabalin + placebo or pregabalin + NAC group for 8 weeks (pregabalin at a dose of 150 mg per day, NAC and matched placebo at doses of 600 mg twice a day). Mean pain score was evaluated at baseline, week 1, 2, 4, 6, and 8 of the study based on the mean 24 hr average pain score, using an 11-point numeric rating scale (NRS). As secondary efficacy measures, mean sleep interference score (SIS) resulting from PDN, responder rates, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety were also assessed. Additionally, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNinety patients completed the eight-week course of the study. The decrease in mean pain scores and mean sleep interference score in pregabalin + NAC group was greater in comparison with pregabalin + placebo group (p value<0.001 in both conditions). Moreover, more responders (defined as ≥50% reduction in mean pain score from baseline to end-point) were observed in the pregabalin + NAC group, in comparison with pregabalin + placebo group (72.1% vs 46.8%). More improvement in PGIC and CGIC from baseline to the end of the study was reported in pregabalin + NAC group. Oral NAC had minimal adverse effects and was well tolerated in almost all patients. Furthermore, in respect to OTS biomarkers, adjuvant NAC significantly decreased serum level of MDA and significantly increased serum levels of SOD, GPx, TAC, and TTG.ConclusionThe pattern of results suggests that compared to placebo and over a time period of 8 weeks, adjuvant NAC is more efficacious in improving neuropathic pain associated with diabetic neuropathy than placebo. Ameliorative effects of NAC on OTS biomarkers demonstrated that NAC may alleviate painful symptoms of diabetic neuropathy, at least in part by its antioxidant effects.

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Section: Discussionmentioning

confidence: 93%

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy

Heidari¹,

Sajedi²,

Mohammadi³

et al. 2019

JPR

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“…Third, by breaking thiolated proteins and releasing free thiols, NAC can regulate the redox state. 51 Beneficial effects of NAC on oxidative stress biomarkers in various pathological conditions such as pneumonia, 26 rheumatoid arthritis, 27 diabetes mellitus, 52 and myocardial infarction 53 have been reported in previous studies. NAC's influence on oxidative stress biomarkers during brain injury also has been investigated in some experimental studies.…”

Section: Discussionmentioning

confidence: 69%

“…25 Both animal and human studies have further confirmed the favorable influence of NAC treatment on inflammatory and OTS biomarkers. [26][27][28] Due to its ability in modulating oxidative stress and inflammatory conditions, recently therapeutic effects of NAC over a wide range of disorders have been investigated. 24 Previous preclinical studies have demonstrated the potential neuroprotective effects of NAC in treatment of various neurodegenerative diseases such as Huntington's disease, 29 Alzheimer's disease, 30 and Parkinson's disease.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke

Sabetghadam¹,

Mazdeh²,

Abolfathi³

et al. 2020

NDT

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Purpose: Numerous preclinical studies have demonstrated the potential neuroprotective effects of N-acetylcysteine (NAC) in the treatment of brain ischemia. Accordingly, the present study aimed to assess the potential therapeutic effects of oral NAC in patients with acute ischemic stroke. Patients and Methods: In a randomized, double-blind, placebo-controlled trial study, 68 patients with acute ischemic stroke with the onset of symptoms less than 24 hours were randomly assigned to either the NAC-treated group or placebo-treated group. NAC and matched placebo were administrated by a 72-hour oral protocol (initially 4 grams loading dose and after on, 4 g in 4 equal divided doses for more 2 days). The primary outcomes were quantification of any neurologic deficit by the use of the National Institute of Health Stroke Scale (NIHSS) score and functional disability by the use of the modified Rankin scale (mRS) at 90 days after stroke. Additionally, serum levels of markers of oxidative stress and inflammation as a main mechanism of its action were assessed at baseline and the end of 3-day treatment protocol. Results: NAC-treated patients in comparison with placebo-treated patients showed a significantly lower mean NIHSS scores at day 90 after stroke. A favorable functional outcome which was defined as an mRS score of 0 or 1, also in favor of NAC compared to placebo was noted on day 90 after stroke (57.6% in the NAC-treated group compared with 28.6% in the placebo-treated group). Further, compared to the placebo, NAC treatment significantly decreased serum levels of proinflammatory biomarkers such as interleukin 6 (IL-6), soluble intercellular cell adhesion molecule-1 (sICAM-1), nitric oxide (NO), malondialdehyde (MDA), and neuron-specific enolase (NSE) and significantly increased serum levels of anti-oxidant biomarkers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and total thiol groups (TTG). Conclusion: The pattern of results suggests that oral NAC administration early after an acute ischemic stroke is associated with a better outcome profile in terms of acute neurological deficit and disability grade compared to placebo. NAC may improve neurological outcomes of patients with stroke at least in part by its antioxidant and anti-inflammatory effects.

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“…Reporting. Only 6 RCTs [16,17,26,27,[31][32][33] describe the implementation process of the blind method and were rated as low risk of bias. Four RCTs [18,24,25,44,46] did not describe the implementation process of blinding, and the indicators of this study are biochemical indicators (such as MDA); they are assessed as low risk of bias.…”

Section: Blinding Incomplete Outcome Data and Selectivementioning

confidence: 99%

“…Therefore, research on oxidative stress, SOD antioxidation, and regulation relationship in patients with RA can reveal the pathological mechanism of RA and find new anti-RA drugs. At present, many randomized controlled trials (RCTs) of antioxidants [16][17][18][19][20] in the treatment of RA patients have been published. However, the results and interventions of these RCTs are diverse, and the quality of the evidence provided varies, which cannot provide clinical doctors with evidence to formulate treatment measures against oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta‐analysis of Randomized Controlled Trials

Zeng

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Objective. To explore the efficacy of antioxidative stress therapy on oxidative stress levels in rheumatoid arthritis (RA) by a systematic review and meta-analysis of randomized controlled trials. Methods. Chinese and English databases such as PubMed, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature were searched, mainly searching for clinical randomized controlled trials of antioxidant therapy for rheumatoid arthritis. The search time is from the establishment of the database to July 2021. Two researchers independently carried out literature search, screening, and data extraction. The bias risk tool provided by the Cochrane Collaboration was used to evaluate the bias risk of all the included literature, and the RevMan 5.3 software was used for meta-analysis. Results. A total of 24 RCTs (28 records) and 1277 participants were included. The time span of randomized controlled trials (RCTs) is from 1986 to 2020. These RCTs involve 14 types of antioxidants or antioxidant therapies, and these therapies have varying degrees of improvement on oxidative stress in RA patients. The summary results showed that the MDA in the experiment group is lower (SMD -0.82, 95% CI -1.35 to -0.28, P = 0.003 ). The difference of TAC, SOD, NO, GPx, CAT, and GSH between two groups was of no statistical significance (TAC (SMD 0.27, 95% CI -0.21 to 0.75, P = 0.27 ), SOD (SMD 0.12, 95% CI -0.16 to 0.40, P = 0.41 ), NO (SMD -2.03, 95% CI -4.22 to 0.16, P = 0.07 ), GPx (SMD 0.24, 95% CI -0.07 to 0.54, P = 0.13 ), CAT (SMD 2.95, 95% CI -2.6 to 8.51, P = 0.30 ), and GSH (SMD 2.46, 95% CI -0.06 to 4.98, P = 0.06 )). For adverse events, the summary results showed that the difference was of no statistical significance (RR 1.16, 95% CI 0.79 to 1.71, P = 0.45 ). In addition, antioxidant therapy has also shown improvement in clinical efficacy indexes (number of tender joints, number of swollen joints, DAS28, VAS, and HAQ) and inflammation indexes (ESR, CRP, TNF-α, and IL6) for RA patients. Conclusion. The existing evidence shows potential benefits, mainly in reducing MDA and increasing TAC and GSH in some subgroups. However, more large samples and higher quality RCTs are needed to provide high-quality evidence, so as to provide more clinical reference information for the antioxidant treatment of RA.

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A Pilot Study to Evaluate the Effects of Oral N-Acetyl Cysteine on Inflammatory and Oxidative Stress Biomarkers in Rheumatoid Arthritis

Cited by 29 publications

References 37 publications

<p>Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy</p>

<p>Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy</p>

<p>Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke</p>

The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta‐analysis of Randomized Controlled Trials

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