scholarly journals Lack of Association between Nuclear Factor Erythroid-Derived 2-Like 2 Promoter Gene Polymorphisms and Oxidative Stress Biomarkers in Amyotrophic Lateral Sclerosis Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Annalisa LoGerfo ◽  
Lucia Chico ◽  
Loredana Borgia ◽  
Lucia Petrozzi ◽  
Anna Rocchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Gene Promoter ◽  
Redox Balance ◽  
Nuclear Factor ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Reducing Ability ◽  
Als Patients ◽  
Lateral Sclerosis

Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients(n=145)and healthy controls(n=168), three SNPs inNrf2gene promoter: −653 A/G, −651 G/A, and −617 C/A and evaluated, in a subset(n=73)of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers.Nrf2polymorphisms were not different among patients and controls. Increased levels of AOPP(P<0.05)and decreased levels of FRAP(P<0.001)have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance andNrf2polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the −653 A/G, −651 G/A, and −617 C/ANrf2SNPs in ALS patients.

scholarly journals Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

2020 ◽  
Vol 21 (3-4) ◽  
pp. 263-272
Author(s):  
Hiroshi Mitsumoto ◽  
Diana C. Garofalo ◽  
Regina M. Santella ◽  
Eric J. Sorenson ◽  
Björn Oskarsson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Plasma Creatinine ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
And Oxidative Stress ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial After Curcumin Supplementation

2018 ◽  
Vol 17 (10) ◽  
pp. 767-779 ◽  
Author(s):  
Lucia Chico ◽  
Elena Caldarazzo Ienco ◽  
Costanza Bisordi ◽  
Annalisa Lo Gerfo ◽  
Lucia Petrozzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Control Group ◽  
Therapeutic Trial ◽  
Entire Study ◽  
Reducing Ability ◽  
Group A ◽  
Group B ◽  
And Oxidative Stress ◽  
Lateral Sclerosis

Objective: To investigate the efficacy of curcumin oral supplementation (600 mg/day, Brainoil), a natural antioxidant compound, in Amyotrophic Lateral Sclerosis (ALS). Methods: Patients were randomized into two groups: Group A received placebo for 3 months, then Brainoil for the following 3 months, Group B took Brainoil for 6 months. The evaluations were conducted at basal (T0), after 3 months of double blinded Brainoil or placebo treatment (T1), and after the 3 month open-label phase (T2). Clinical evaluations and oxidative stress biomarkers, including oxidative protein products (AOPPs), ferric reducing ability (FRAP), total thiols (T-SH) and lactate, were evaluated, compared to a control group, during an incremental forearm exercise test. Results: Over the entire study Group B showed a stable score of the ALS-FRS-r which decreased in Group A (p<0.01), in parallel with a reduction of AOPPs (p<0.01) which was not detected into Group A. Also FRAP exercise values remained stable in Group B, while in Group A they were reduced without treatment at T1 (0.05<p<0.01), for then increase at T2 with introduction of therapy (p<0.05). In Group B T1>T0 exercise lactate was lower compared to Group A (p<0.01). Compared to controls, the whole ALS population showed a greater oxidative stress (p<0.001), those treated with curcumin (Group B) exhibiting decreased exercise AOPPs at T2 with values approaching those of controls. Conclusion: Although further studies are needed to confirm these data, treatment with curcumin shows encouraging results indicating a slight slowdown in disease progression, improving aerobic metabolism and oxidative damage, this also contributing to deepen knowledge into the pathogenic mechanisms of ALS.

Neuroprotective potential of adenyl cyclase/cAMP/CREB and mitochondrial CoQ10 activator in amyotrophic lateral sclerosis rats

2020 ◽  
Vol 16 ◽  
Author(s):  
Mohmmad Mamtaj Alam ◽  
Elijabeth Minj ◽  
Rajeshwar Kumar Yadav ◽  
Sidharth Mehan
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Drug Therapy ◽  
Therapeutic Approach ◽  
Methyl Mercury ◽  
Chronic Treatment ◽  
Adenyl Cyclase ◽  
Als Patients ◽  
And Oxidative Stress ◽  
Lateral Sclerosis

Aim: To investigate neuroprotective potential of of forskolin (FSK) in combination with solanesol (SNL) along with clinically proven drugs (riluzole, baclofen, citalopram) on behavioral, molecular and neurochemical alterations in methyl mercury-induced amyotrophic lateral sclerosis (ALS) rats. Background: ALS is a motor neuron disease in which oxidative stress is the principle mechanism ofneuronal death which can be mimicked by the dominant mutations in an antioxidant enzyme SOD-1. Due to MeHg neurotoxicity, behavioral and neurochemical alterations occur in rats. During ALS mitochondrial CoQ10 dysfunctioning and downregulation of adenyl cyclase/CREB are major pathological hallmark for neurodegeneration in ALS. Clinically proven drug therapy comes with limited therapeutic involvement, and is used as approachable therapy in ALS patients. Objective: Therefore, current research explores the up-regulation of adenyl cyclase/cAMP/CREB by FSK 30, 60 mg/kg in combination with mitochondrial ETC-coenzyme-Q10 precursor SNL 15, 30 mg/kg can be a preventive therapeutic approach to overcome the ALS like symptoms. Method: MeHg (5 mg/kg) is a neurotoxic compound that leads to ALS like behavioral & neurochemical alterations. Results: Chronic treatment with the combination of FSK 30,60 mg/kg and SNL 15,30 mg/kg alone and along with standard drugs citalopram (5 mg/kg), riluzole (5 mg/kg) and baclofen (3 mg/kg) increased the adenyl cyclase and mitochondrial CoQ10 and ETC-complexes enzyme levels and shows the neuroprotective potential by significantly improving the cognitive deficitslocomotion, , grip strength, and restoration of neurochemicals alterations along with reducing the level of inflammatory mediators and oxidative stress in ALS rats. Conclusion: Thus, we concluded that FSK in combination with SNL along with standard drugs can be a possible therapeutic approach for the treatment of ALS.

scholarly journals Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways

2011 ◽  
Vol 208 (12) ◽  
pp. 2429-2447 ◽  
Author(s):  
Vivek Swarup ◽  
Daniel Phaneuf ◽  
Nicolas Dupré ◽  
Susanne Petri ◽  
Michael Strong ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Messenger Rna ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Healthy Individuals ◽  
Wild Type ◽  
Disease Symptoms ◽  
Als Patients ◽  
Lateral Sclerosis

TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease.

scholarly journals No association of GSTP1 rs1695 polymorphism with amyotrophic lateral sclerosis: A case-control study in the Brazilian population

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247024
Author(s):  
Jéssica Barletto de Sousa Barros ◽  
Kamilla de Faria Santos ◽  
Rômulo Morais Azevedo ◽  
Rayana Pereira Dantas de Oliveira ◽  
Ana Carolina Dourado Leobas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Case Control Study ◽  
Case Control ◽  
Demographic Characteristics ◽  
Genetic Inheritance ◽  
Central Population ◽  
Als Patients ◽  
Control Study ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease that affects motor neurons and promotes progressive muscle atrophy. It has a multifactorial etiology, where environmental conditions playing a remarkable role through the increase of oxidative stress. Genetic polymorphisms in cell detoxification genes, such as Glutathione S-Transferase Pi 1 (GSTP1) can contribute to excessive oxidative stress, and therefore may be a risk factor to ALS. Thus, this study aimed to investigate the role of the GSTP1 rs1695 polymorphism in ALS susceptibility in different genetic inheritance models and evaluate the association of the genotypes with risk factors, clinical and demographic characteristics of ALS patients from the Brazilian central population. This case-control study was conducted with 101 patients with ALS and 101 healthy controls. GSTP1 rs1695 polymorphism genotyping was performed with Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP). The statistical analysis was carried out using the SPSS statistical package and SNPStats software. Analysis of genetic inheritance models was performed by logistic regression, which was used to determine the Odds Ratio. The results of this first study in the Brazilian population demonstrated that there was no risk association between the development of ALS and the GSTP1 rs1695 polymorphism in any genetic inheritance model (codominant, dominant, recessive, overdominant, and logarithmic); and that the polymorphic variants were not associated with the clinical and demographic characteristics of ALS patients. No association of the GSTP1 rs1695 polymorphism and ALS development in the Brazilian central population was found. These findings may be justified by the multifactorial character of the disease.

Hypothyroidism induces oxidative stress and DNA damage in breast

2021 ◽  
Author(s):  
Milena Simões Peixoto ◽  
Andressa de Vasconcelos e Souza ◽  
Iris Soares Andrade ◽  
Carolina de Carvalho el Giusbi ◽  
Caroline Coelho Faria ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Dna Damage ◽  
Genomic Instability ◽  
Redox Balance ◽  
Ros Generation ◽  
Antioxidant Enzyme Activities ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Mcf10a Cells

Breast cancer and thyroid dysfunctions have been associated for decades. Although many studies suggest a biological correlation, the mechanisms linking these two pathologies have not been elucidated. Reactive oxygen species (ROS) can oxidize lipids, proteins, and DNA molecules and may promote tumor initiation. Hence, we aimed at evaluating the mammary redox balance and genomic instability in a model of experimental hypothyroidism. Female Wistar rats were treated with 0.03% methimazole for 7 or 21 days to evaluate ROS generation, antioxidant enzyme activities, and oxidative stress biomarkers, as well as genomic instability. After 7 days, lower catalase, GPx, and DUOX activities were detected in the breast of hypothyroid group compared to the control while the levels of 4-hydroxynonenal (HNE) were higher. In addition, hypothyroid group showed an increase in γH2Ax/H2Ax ratio. 21-days hypothyroid group had increased catalase and SOD activities, without significant differences between groups in the levels of oxidative stress biomarkers and DNA damage. TSH-treated MCF10A cells showed a higher extracellular, intracellular, and mitochondrial ROS production. Additionally, greater DNA damage was observed in these cells, demonstrated by a higher comet tail DNA percentage and increased 53BP1 foci. Finally, we found that TSH treatment was not able to alter cell viability. The Genome Cancer Atlas (TGCA) data showed that high TSHR expression is associated with more invasive breast cancer types. In conclusion, we demonstrate that oxidative stress and DNA damage in breast are early events of experimental hypothyroidism. Moreover, high TSH levels induce oxidative stress and genomic instability in mammary cells.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

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