PMID: 

Int J Mol Sci. 2019 Dec 25 ;21(1). Epub 2019 Dec 25. PMID: 31881712

Abstract Title: 

Therapeutic Potential offor Depressive Disorder.

Abstract: 

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects.also known as Lion's mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson's disease, and Alzheimer's disease. Bioactive compounds extracted from the mycelia and fruiting bodies ofhave been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects ofhave not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression,may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits ofas a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

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PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Nov 25. Epub 2019 Nov 25. PMID: 31768573

Abstract Title: 

Effects of N-acetylcysteine amide on anxiety and stress behavior in zebrafish.

Abstract: 

Anxiety disorders are highly prevalent and a leading cause of disability worldwide. Their etiology is related to stress, an adaptive response of the organism to restore homeostasis, in which oxidative stress and glutamatergic hyperactivity are involved. N-Acetylcysteine (NAC) is a multitarget approved drug proved to be beneficial in the treatment of various mental disorders. Nevertheless, NAC has low membrane permeability and poor bioavailability and its limited delivery to the brain may explain inconsistencies in the literature. N-Acetylcysteine amide (AD4) is a synthetic derivative of NAC in which the carboxyl group was modified to an amide. The amidation of AD4 improved lipophilicity and blood-brain barrier permeability and enhanced its antioxidant properties. The purpose of this study was to investigate the effects of AD4 on behavioral and biochemical parameters in zebrafish anxiety models. Neither AD4 nor NAC induced effects on locomotion and anxiety-related parameters in the novel tank test. However, in the light/dark test, AD4 (0.001 mg/L) increased the time spent in the lit side in a concentration 100 times lower than NAC (0.1 mg/L). In the acute restraint stress protocol, NAC and AD4 (0.001 mg/L) showed anxiolytic properties without meaningful effects on oxidative status. The study suggests that AD4 has anxiolytic effects in zebrafish with higher potency than the parent compound. Additional studies are warranted to characterize the anxiolytic profile of AD4 and its potential in the management of anxiety disorders.

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PMID: 

Antioxidants (Basel). 2019 Nov 24 ;8(12). Epub 2019 Nov 24. PMID: 31771272

Abstract Title: 

N-acetylcysteine Decreases Fibrosis and Increases Force-Generating Capacity ofDiaphragm.

Abstract: 

Respiratory muscle weakness occurs due to dystrophin deficiency in Duchenne muscular dystrophy (DMD). Themouse model of DMD shows evidence of impaired respiratory muscle performance with attendant inflammation and oxidative stress. We examined the effects of N-acetylcysteine (NAC) supplementation on respiratory system performance inmice. Eight-week-old male wild type (= 10) and(= 20) mice were studied; a subset of(= 10) received 1% NAC in the drinking water for 14 days. We assessed breathing, diaphragm, and external intercostal electromyogram (EMG) activities and inspiratory pressure during ventilatory and non-ventilatory behaviours. Diaphragm muscle structure and function, cytokine concentrations, glutathione status, and mRNA expression were determined. Diaphragm force-generating capacity was impaired incompared with wild type. Diaphragm muscle remodelling was observed in, characterized by increased muscle fibrosis, immune cell infiltration, and central myonucleation. NAC supplementation rescueddiaphragm function. Collagen content and immune cell infiltration were decreased in+ NAC compared withdiaphragms. The cytokines IL-1β, IL-6 and KC/GRO were increased inplasma and diaphragm compared with wild type; NAC decreased systemic IL-1β and KC/GRO concentrations inmice. We reveal that NAC treatment improveddiaphragm force-generating capacity associated with beneficial anti-inflammatory and anti-fibrotic effects. These data support the potential use of NAC as an adjunctive therapy in human dystrophinopathies.

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PMID: 

J Child Adolesc Psychopharmacol. 2019 Dec 3. Epub 2019 Dec 3. PMID: 31800306

Abstract Title: 

N-Acetylcysteine for Pediatric Obsessive-Compulsive Disorder: A Small Pilot Study.

Abstract: 

Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD.We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo.Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test:(37) = 2.36, = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 outof 5 participants achieved>35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group.Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

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PMID: 

J Pain Res. 2019 ;12:3147-3159. Epub 2019 Nov 19. PMID: 31819599

Abstract Title: 

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

Abstract: 

Purpose: Painful 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 methods: 113 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.Results: Ninety 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

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PMID: 

Sci Rep. 2019 Dec 10 ;9(1):18741. Epub 2019 Dec 10. PMID: 31822750

Abstract Title: 

Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

Abstract: 

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

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PMID: 

Aust N Z J Psychiatry. 2019 Dec 11:4867419893439. Epub 2019 Dec 11. PMID: 31826654

Abstract Title: 

Meta-analysis of randomised controlled trials with-acetylcysteine in the treatment of schizophrenia.

Abstract: 

OBJECTIVE: There is accumulating evidence that adjunctive treatment with-acetylcysteine may be effective for schizophrenia. This study aimed to conduct a comprehensive meta-analysis examining the efficacy of randomised control trials investigating-acetylcysteine as an adjunct treatment for schizophrenia and the first to investigate cognition as an outcome.METHODS: We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of-acetylcysteine for schizophrenia. We undertook pairwise meta-analyses of-acetylcysteine vs placebo for psychosis symptoms and cognition.RESULTS: Seven studies, including= 220 receiving-acetylcysteine and= 220 receiving placebo, met inclusion criteria for the pairwise meta-analyses. Positive and Negative Syndrome Scale negative and total scores were significantly improved in the-acetylcysteine group after 24 weeks of treatment. The cognitive domain of working memory improved with-acetylcysteine supplementation.CONCLUSION: Evidence supports the notion that-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Treatment effects were observed at the later time point (⩾24 weeks), suggesting that longer interventions are required for the success of-acetylcysteine treatment.

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PMID: 

Cureus. 2019 Nov 5 ;11(11):e6073. Epub 2019 Nov 5. PMID: 31832291

Abstract Title: 

N-acetylcysteine in the Management of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Abstract: 

Introduction Chronic obstructive pulmonary disease (COPD) is a preventable disease of the airways characterized by limited airflow. Acute exacerbations of COPD (AECOPD) may be precipitated by noxious stimuli. N-acetylcysteine (NAC) has mucolytic, antioxidant, and anti-inflammatory activity. We conducted this study to evaluate the effect of adding high-dose NAC to the protocol treatment of AECOPD. Methods In this single-center, prospective, interventional study, patients admitted with AECOPD, airflow obstruction on spirometry, and who were current smokers with 10 or more packs per year were included after attaining informed consent. NAC granules 600 mg twice daily orally (high dose) were included in the regimen of 25 randomly selected patients and the other 25 were managed without NAC. An improvement in clinical and biochemical markers was observed on day three and day seven. For statistical analysis, SPSS for Windows version 21.0 (IBM Corp., Armonk, NY) was utilized. Results The study was completed by 21 patients in the NAC group and 19 in the non-NAC group. In the NAC group, there was a significant improvement in the mean partial pressure of oxygen (PaO) both on day three (p=0.03) and day seven (p=0.01). The mean partial pressure of carbon dioxide (PaCO) was at the borderline in the two groups on day three; however, on day seven, the NAC group showed significantly improved PaCOas compared to the non-NAC group (p=0.007). There were significant improvements in oxygen saturation of the NAC group on day seven (p=0.02). There were significant improvements in clinical signs, including wheezing and dyspnea and the need for nasal oxygen support (p≤0.05). Conclusion The addition of 600 mg twice daily NAC (high dose) to the protocol treatment of patients with acute exacerbation of COPD may have beneficial outcomes. In the future, the role of high-dose NAC in AECOPD must be studied through multicenter, double-blinded, placebo-controlled trials with larger sample sizes in order to either establish or invalidate this association.

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PMID: 

Biomolecules. 2019 Dec 17 ;9(12). Epub 2019 Dec 17. PMID: 31861240

Abstract Title: 

-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats.

Abstract: 

Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin.

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PMID: 

Antiviral Res. 2019 Dec 26:104699. Epub 2019 Dec 26. PMID: 31883926

Abstract Title: 

N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response.

Abstract: 

Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective specific treatment is available presently. Our previous study demonstrated that suppression of proinflammatory caspase-1 activation effectively inhibited CVB replication. N-acetyl cysteine (NAC) is a widely used antioxidant. In this study, we found that NAC significantly alleviated the myocardial injury caused by CVB type 3 (CVB3) under in vivo condition. Importantly, NAC treatment simultaneously suppressed viral replication and inflammatory response in both myocardium and cell culture. The antiviral and anti-inflammation mechanism of NAC, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which further contributes to caspase-1 down-regulation. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB and anti-inflammation effect through targeting caspase-1. Given that NAC is a clinically approved medicine, we recommend NAC as a valuable therapeutic agent for viral myocarditis caused by CVB.

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