scholarly journals What is a Therapeutic Potential of N-Acetylcysteine in Lung Silicosis?

2021 ◽  
Vol 21 (3) ◽  
pp. 80-89
Author(s):  
Adamcakova Jana ◽  
Mokra Daniela
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Silicon Dioxide ◽  
Pulmonary Disease ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Clinical Use ◽  
Fundamental Factor ◽  
Long Term Experience

Abstract Lung silicosis is a serious pulmonary disease caused by an exposure of lung to inhaled silicon dioxide (SiO2) or silica. Although pathomechanisms of the disease have not been fully elucidated, oxidative stress has been recognized as a fundamental factor triggering a fibrotizing inflammation leading to irreversible changes in lung tissue. Based on this knowledge, therapeutic potential of various antioxidants has been intensively discussed. Among them, N-acetylcysteine with its multiple anti-inflammatory and antioxidant actions and a long-term experience with its clinical use in various diseases appears as a very promising choice. The purpose of this article is to review the therapeutic effects of N-acetylcysteine particularly in relation to a lung injury and to point out a potential of N-acetylcysteine in the treatment of lung silicosis.

scholarly journals The nanocomposite fullerol reduces oxidative stress, pulmonary injury, and mortality in a rat model of acute lung injury

2021 ◽  
Author(s):  
Rosária Aires ◽  
Ildernandes Vieira-Alves ◽  
Leda Maria Coimbra-Campos ◽  
Marina Ladeira ◽  
Teresa Socarras ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
High Mortality ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mortality Rates ◽  
Kaplan Meier ◽  
Pulmonary Damage

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10 to 10 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

scholarly journals N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1283
Author(s):  
Phiwayinkosi V. Dludla ◽  
Bongani B. Nkambule ◽  
Sithandiwe E. Mazibuko-Mbeje ◽  
Tawanda M. Nyambuya ◽  
Fabio Marcheggiani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Accumulation ◽  
Randomized Clinical Trials ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Metabolic Complications ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Acetyl Cysteine

Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

scholarly journals Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis

2019 ◽  
Vol 20 (16) ◽  
pp. 4057 ◽  
Author(s):  
Yu Chiuan Wu ◽  
Han Hsiang Huang ◽  
Yi Jhen Wu ◽  
Ioannis Manousakas ◽  
Chin Chang Yang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Water Solubility ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Liver Injuries ◽  
Repeated Consumption ◽  
Histopathologic Findings ◽  
Poor Stability

Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 ± 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.

scholarly journals Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Tsung-Hsun Hsieh ◽  
Xiao-Kuo He ◽  
Hui-Hua Liu ◽  
Jia-Jin J. Chen ◽  
Chih-Wei Peng ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Magnetic Stimulation ◽  
Therapeutic Potential ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Motor Functions

Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson’s disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.

scholarly journals Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 198 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Han-Gyo Shin ◽  
Seong-Hun Jeong ◽  
Da-Bin Jeon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Herbal Remedy ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tnf Α

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

scholarly journals Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L217-L230 ◽  
Author(s):  
Márcia Isabel Bittencourt-Mernak ◽  
Nathalia M. Pinheiro ◽  
Fernanda P. R. Santana ◽  
Marina P. Guerreiro ◽  
Beatriz M. Saraiva-Romanholo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Function ◽  
Lung Injury ◽  
Collagen Fiber ◽  
Pulmonary Inflammation ◽  
Fiber Formation ◽  
Therapeutic Effects ◽  
Therapeutic Treatment ◽  
Fiber Deposition

Sakuranetin is the main isolate flavonoid from Baccharis retusa ( Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-κB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-κB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-α and IL-1β in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.

scholarly journals Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease

2015 ◽  
Vol 309 (10) ◽  
pp. L1037-L1040 ◽  
Author(s):  
Gerry T. M. Wagenaar ◽  
Pieter S. Hiemstra ◽  
Reinoud Gosens
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Guanylate Cyclase ◽  
Premature Birth ◽  
Soluble Guanylate Cyclase ◽  
Therapeutic Potential ◽  
Vascular Development ◽  
Supplemental Oxygen ◽  
Neonatal Lung

Supplemental oxygen after premature birth results in aberrant airway, alveolar, and pulmonary vascular development with an increased risk for bronchopulmonary dysplasia, and development of wheeze and asthma, pulmonary hypertension, and chronic obstructive pulmonary disease in survivors. Although stimulation of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway has significant beneficial effects on disease development in animal models, so far this could not be translated to the clinic. Oxidative stress reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in inactivation or degradation of sGC. Reduced sGC activity and/or expression is associated with pathology due to premature birth, oxidative stress-induced lung injury, including impaired alveolar maturation, smooth muscle cell (SMC) proliferation and contraction, impaired airway relaxation and vasodilation, inflammation, pulmonary hypertension, right ventricular hypertrophy, and an aggravated response toward hyperoxia-induced neonatal lung injury. Recently, Britt et al. (10) demonstrated that histamine-induced Ca2+ responses were significantly elevated in hyperoxia-exposed fetal human airway SMCs compared with normoxic controls and that this hyperoxia-induced increase in the response was strongly reduced by NO-independent stimulation and activation of sGC. These recent studies highlight the therapeutic potential of sGC modulators in the treatment of preterm infants for respiratory distress with supplemental oxygen. Such treatment is aimed at improving aberrant alveolar and vascular development of the neonatal lung and preventing the development of wheezing and asthma in survivors of premature birth. In addition, these studies highlight the suitability of fetal human airway SMCs as a translational model for pathological airway changes in the neonate.

scholarly journals Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4815
Author(s):  
Vilde Yuli Stenberg ◽  
Roy Hartvig Larsen ◽  
Li-Wei Ma ◽  
Qian Peng ◽  
Petras Juzenas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mouse Models ◽  
Cytotoxic Effect ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Radiation Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Tumour Spheroid ◽  
Multicellular Tumour Spheroid

Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001.

scholarly journals Bixin protects against particle-induced long-term lung injury in an NRF2-dependent manner

2018 ◽  
Vol 7 (2) ◽  
pp. 258-270 ◽  
Author(s):  
Lian Xue ◽  
Hong Zhang ◽  
Jie Zhang ◽  
Bingyan Li ◽  
Zengli Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Disease ◽  
Dependent Manner

Scope: Particle-induced lung injury is a kind of comprehensive pulmonary disease with not only inflammation but also fibrosis.

scholarly journals Nrf2 activation as a future target of therapy for chronic diseases

2014 ◽  
Vol 4 (12) ◽  
pp. 510 ◽  
Author(s):  
Rame Taha ◽  
Gilbert Blaise
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Premature Aging ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nrf2 Activation ◽  
Inflammatory Drugs ◽  
Therapeutic Alternatives

Background: Chronic inflammation integrally related to oxidative stress has been increasingly recognized as a contributing factor in various chronic diseases such as neurodegenerative diseases, pulmonary diseases, metabolic syndrome, and cardiovascular diseases as well as premature aging. Thus, inhibiting this vicious circle has the potential to delay, prevent progression, and treat those diseases. However, adverse effects of current anti-inflammatory drugs and the failure of exogenous antioxidant encourage scientists to develop new therapeutic alternatives. The nuclear factor E2-related factor 2 (Nrf2) is the transcription factor that is responsible for the expression of antioxidant response element (ARE)-regulated genes and have been described as having many therapeutic effects. In this review, we have discussed the role of oxidative stress in various chronic diseases. Furthermore, we have also explored various novel ways to activate Nrf2 either directly or indirectly, which may have therapeutic potential in attenuating oxidative stress, inflammation and mitochondrial dysfunction that contributes to chronic diseases.Keywords: Oxidative stress, Mitochondria, Inflammation, Nrf2, Nutrition, Chronic diseases

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