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La Revue de Medecine Interne Nov 2023Amatoxin-containing mushroom poisoning occurs after consumption of certain mushroom species, of the genera Amanita, Lepiota and Galerina. Amanita phalloides is the most... (Review)
Review
Amatoxin-containing mushroom poisoning occurs after consumption of certain mushroom species, of the genera Amanita, Lepiota and Galerina. Amanita phalloides is the most implicated species, responsible for over more than 90% of mushroom-related deaths. The α-amanitin is responsible for most of the observed effects. Symptoms are characterized by severe delayed gastrointestinal disorders (more than six hours after ingestion). The liver being the main target organ, outcome is marked by an often severe hepatitis which can evolve towards terminal liver failure, justifying orthotopic liver transplantation. Acute renal failure is common. Diagnosis of amatoxin-containing mushroom poisoning is based primarily on clinical data; it can be biologically confirmed using detection of amatoxins, especially from urine samples. In the absence of an antidote, early hospital management is essential. It is based on supportive care (early compensation of hydroelectrolytic losses), gastrointestinal digestive decontamination, elimination enhancement, amatoxin uptake inhibitors and antioxidant therapy. Combined therapy associating silibinin and N-acetylcysteine is recommended. Prognosis of this severe poisoning has greatly benefited from improved resuscitation techniques. Mortality is currently less than 10%. In the event of a suspected or confirmed case, referral to a Poison Control Center is warranted in order to establish the diagnosis and guide the medical management of patients in an early and appropriate way.
PubMed: 37949692
DOI: 10.1016/j.revmed.2023.10.459 -
Mitochondrion Sep 2023Mitochondrial Complex I dysfunction and oxidative stress have been part of the pathophysiology of several diseases ranging from mitochondrial disease to chronic diseases...
Mitochondrial Complex I dysfunction and oxidative stress have been part of the pathophysiology of several diseases ranging from mitochondrial disease to chronic diseases such as diabetes, mood disorders and Parkinson's Disease. Nonetheless, to investigate the potential of mitochondria-targeted therapeutic strategies for these conditions, there is a need further our understanding on how cells respond and adapt in the presence of Complex I dysfunction. In this study, we used low doses of rotenone, a classical inhibitor of mitochondrial complex I, to mimic peripheral mitochondrial dysfunction in THP-1 cells, a human monocytic cell line, and explored the effects of N-acetylcysteine on preventing this rotenone-induced mitochondrial dysfunction. Our results show that in THP-1 cells, rotenone exposure led to increases in mitochondrial superoxide, levels of cell-free mitochondrial DNA, and protein levels of the NDUFS7 subunit. N-acetylcysteine (NAC) pre-treatment ameliorated the rotenone-induced increase of cell-free mitochondrial DNA and NDUFS7 protein levels, but not mitochondrial superoxide. Furthermore, rotenone exposure did not affect protein levels of the NDUFV1 subunit but induced NDUFV1 glutathionylation. In summary, NAC may help to mitigate the effects of rotenone on Complex I and preserve the normal function of mitochondria in THP-1 cells.
Topics: Humans; Acetylcysteine; Rotenone; THP-1 Cells; Superoxides; Oxidative Stress; Electron Transport Complex I; DNA, Mitochondrial; Reactive Oxygen Species
PubMed: 37419232
DOI: 10.1016/j.mito.2023.07.001 -
Experimental and Clinical Endocrinology... Dec 2023Painful diabetic neuropathy (PDN) is a serious and very common complication of diabetes mellitus (DM). It negatively affects the quality of life, increases morbidity and... (Review)
Review
Painful diabetic neuropathy (PDN) is a serious and very common complication of diabetes mellitus (DM). It negatively affects the quality of life, increases morbidity and poses a financial burden on the health care system. Currently, treatment of PDN focuses on glycaemic control, while pathogenesis-oriented therapy has not yielded satisfactory results. The need to improve therapy remains. There is accumulating evidence on the potential benefit of nutritional interventions. This narrative review aims to examine the potential benefit of dietary and nutritional supplementation for PDN management. According to the preliminary research, supplementation with vitamin E, B-complex, omega-3 fatty acids, CoQ10 or N-acetylcysteine seems to be associated with promising results in improving PDN symptoms.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Dietary Supplements; Diet; Vitamin E; Diabetes Mellitus
PubMed: 37813369
DOI: 10.1055/a-2188-1745 -
Advanced Healthcare Materials Sep 2023Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as...
Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as nanomaterials with enzyme-like activity, can regulate intro-cellular ROS levels. In this study, a new carbon dots nanozyme, N-acetylcysteine-derived carbon dots (NAC-CDs), is developed and proved to be an ideal antioxidant and anti-senescent agent in IVDD management. The results confirmed the NAC-CDs have satisfactory biocompatibility and strong superoxide dismutase (250 U mg ), catalase, glutathioneperoxidase-like activity, and total antioxidant capacity. Then, the powerful free radical scavenging and antioxidant ability of NAC-CDs are demonstrated in vitro as observing the reduced ROS in H O induced senescent nucleus pulposus cells (NPCs), in which the elimination efficiency of toxic ROS is more than 90%. NAC-CDs also maintained mitochondrial homeostasis and suppressed cellular senescence, subsequently inhibited the expression of inflammatory factors in NPCs. In vivo, evaluations of imaging and tissue morphology assessments suggested that disc height index, magnetic resonance imaging grade and histological score are significantly improved from the degenerative models when NAC-CDs is applied. In conclusion, the study developed a novel carbon dots nanozyme, which efficiently rescues IVDD from ROS induced NPCs senescence and provides a potential strategy in management of IVDD in clinic.
Topics: Humans; Intervertebral Disc Degeneration; Acetylcysteine; Antioxidants; Reactive Oxygen Species; Nucleus Pulposus
PubMed: 37256605
DOI: 10.1002/adhm.202300533 -
Italian Journal of Pediatrics Jul 2023To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the...
BACKGROUND
To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP).
METHODS
Eighty-two RMPP patients admitted to Pediatrics at The First People's Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups.
RESULTS
The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05).
CONCLUSIONS
BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.
Topics: Child; Humans; Mycoplasma pneumoniae; Acetylcysteine; Retrospective Studies; Budesonide; Ambroxol; Pneumonia, Mycoplasma
PubMed: 37422684
DOI: 10.1186/s13052-023-01491-y -
Current Opinion in Ophthalmology Jan 2024Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract... (Review)
Review
PURPOSE OF REVIEW
Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract development and key biomarkers - glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) - to clarify their functions and potential applications in predictive diagnostics and therapies.
RECENT FINDINGS
Antioxidants serve as pivotal markers in cataract pathogenesis. GSH affects the central lens due to factors such as enzyme depletion and altered connexin expression, impairing GSH diffusion. Age-related oxidative stress may hinder GSH transport via connexin channels or an internal microcirculation system. N-acetylcysteine, a GSH precursor, shows promise in mitigating lens opacity when applied topically. Additionally, SOD, particularly SOD1, correlates with increased cataract development and gel formulations have exhibited protective effects against posterior subscapular cataracts. Lastly, markers of lipid peroxidation, MDA and 4-HNE, have been shown to reflect disease severity. Studies suggest a potential link between 4-HNE and connexin channel modification, possibly contributing to reduced GSH levels.
SUMMARY
Oxidative stress is a significant contributor to cataract development, underscoring the importance of antioxidants in diagnosis and treatment. Notably, GSH depletion, SOD decline, and lipid peroxidation markers are pivotal factors in cataract pathogenesis, offering promising avenues for both diagnosis and therapeutic intervention.
Topics: Humans; Antioxidants; Oxidative Stress; Cataract; Lens, Crystalline; Glutathione; Superoxide Dismutase; Connexins
PubMed: 37882550
DOI: 10.1097/ICU.0000000000001009 -
Respiratory Research Jul 2023Oxidative stress and persistent airway inflammation are thought to be important contributors to the development of chronic obstructive pulmonary disease (COPD). This... (Review)
Review
BACKGROUND
Oxidative stress and persistent airway inflammation are thought to be important contributors to the development of chronic obstructive pulmonary disease (COPD). This review summarizes the evidence for targeting oxidative stress and inflammation in patients with COPD with mucolytic/antioxidant thiols and inhaled corticosteroids (ICS), either alone or in combination.
MAIN BODY
Oxidative stress is increased in COPD, particularly during acute exacerbations. It can be triggered by oxidant air pollutants and cigarette smoke and/or by endogenous reactive oxygen species (ROS) released from mitochondria and activated inflammatory, immune and epithelial cells in the airways, together with a reduction in endogenous antioxidants such as glutathione (GSH). Oxidative stress also drives chronic inflammation and disease progression in the airways by activating intracellular signalling pathways and the release of further inflammatory mediators. ICS are anti-inflammatory agents currently recommended for use with long-acting bronchodilators to prevent exacerbations in patients with moderate-to-severe COPD, especially those with eosinophilic airway inflammation. However, corticosteroids can also increase oxidative stress, which may in turn reduce corticosteroid sensitivity in patients by several mechanisms. Thiol-based agents such as erdosteine, N-acetyl L-cysteine (NAC) and S-carboxymethylcysteine (S-CMC) are mucolytic agents that also act as antioxidants. These agents may reduce oxidative stress directly through the free sulfhydryl groups, serving as a source of reducing equivalents and indirectly though intracellular GSH replenishment. Few studies have compared the effects of corticosteroids and thiol agents on oxidative stress, but there is some evidence for greater antioxidant effects when they are administered together. The current Global Initiative for Chronic Obstructive Lung Disease (GOLD) report supports treatment with antioxidants (erdosteine, NAC, S-CMC) in addition to standard-of-care therapy as they have been demonstrated to reduce COPD exacerbations. However, such studies have demonstrated that NAC and S-CMC reduced the exacerbation risk only in patients not treated with ICS, whereas erdosteine reduced COPD exacerbations irrespective of concomitant ICS use suggesting that erdosteine has additional pharmacological actions to ICS.
CONCLUSIONS
Further clinical trials of antioxidant agents with and without ICS are needed to better understand the place of thiol-based drugs in the treatment of patients with COPD.
Topics: Humans; Antioxidants; Sulfhydryl Compounds; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Oxidative Stress; Acetylcysteine; Inflammation; Expectorants
PubMed: 37517999
DOI: 10.1186/s12931-023-02500-8 -
Contemporary Clinical Trials Aug 2023Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and...
BACKGROUND
Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis.
METHOD
In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes.
CONCLUSION
Results will inform smoking cessation treatment among dual users of tobacco and cannabis.
CLINICALTRIALS
gov Identifier: NCT04627922.
Topics: Adult; Humans; Smoking Cessation; Cannabis; Acetylcysteine; Tobacco Use Disorder; Randomized Controlled Trials as Topic
PubMed: 37271412
DOI: 10.1016/j.cct.2023.107250 -
Human Psychopharmacology Mar 2024N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders.
METHODS
PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop-out rates.
RESULTS
A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24 weeks and >24 weeks). There was also no statistical difference in drop-out rates between the two groups.
CONCLUSION
For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.
Topics: Humans; Acetylcysteine; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37712506
DOI: 10.1002/hup.2880 -
Life Sciences Sep 2023Type 1 diabetes mellitus (T1DM) has been linked to the occurrence of skeletal muscle atrophy. Insulin monotherapy may lead to excessive blood glucose fluctuations....
AIMS
Type 1 diabetes mellitus (T1DM) has been linked to the occurrence of skeletal muscle atrophy. Insulin monotherapy may lead to excessive blood glucose fluctuations. N-acetylcysteine (NAC), a clinically employed antioxidant, possesses cytoprotective, anti-inflammatory, and antioxidant properties. The objective of our study was to evaluate the viability of NAC as a supplementary treatment for T1DM, specifically regarding its therapeutic and preventative impacts on skeletal muscle.
MAIN METHODS
Here, we used beagles as T1DM model for 120d to explore the mechanism of NRF2/HO-1-mediated skeletal muscle oxidative stress and apoptosis and the therapeutic effects of NAC. Oxidative stress and apoptosis related factors were analyzed by immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR assay.
KEY FINDINGS
The findings indicated that the co-administration of NAC and insulin led to a reduction in creatine kinase levels, preventing weight loss and skeletal muscle atrophy. Improvement in the reduction of muscle fiber cross-sectional area. The expression of Atrogin-1, MuRF-1 and MyoD1 was downregulated, while Myh2 and MyoG were upregulated. In addition, CAT and GSH-Px levels were increased, MDA levels were decreased, and redox was maintained at a steady state. The decreased of key factors in the NRF2/HO-1 pathway, including NRF2, HO-1, NQO1, and SOD1, while KEAP1 increased. In addition, the apoptosis key factors Caspase-3, Bax, and Bak1 were found to be downregulated, while Bcl-2, Bcl-2/Bax, and CytC were upregulated.
SIGNIFICANCE
Our findings demonstrated that NAC and insulin mitigate oxidative stress and apoptosis in T1DM skeletal muscle and prevent skeletal muscle atrophy by activating the NRF2/HO-1 pathway.
Topics: Dogs; Animals; Antioxidants; Acetylcysteine; NF-E2-Related Factor 2; Diabetes Mellitus, Type 1; Kelch-Like ECH-Associated Protein 1; bcl-2-Associated X Protein; Signal Transduction; Oxidative Stress; Muscular Atrophy; Muscle, Skeletal; Proto-Oncogene Proteins c-bcl-2; Apoptosis; Insulins
PubMed: 37495077
DOI: 10.1016/j.lfs.2023.121975