Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

2020 ◽  
Author(s):  
Tiago Elias Allievi Frizon ◽  
José H. Cararo ◽  
Sumbal Saba ◽  
Gustavo C. Dal-Pont ◽  
Monique Michels ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Thiobarbituric Acid ◽  
Positive Control ◽  
Protein Carbonyl ◽  
Oxidative Challenge ◽  
Hydroxy Esters ◽  
Old Mice ◽  
Oxidative Stress Inducer

<p>Herein we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in cultured mouse neurons. First, <i>α</i>-methylene-<i>β</i>-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (<b>3a-f</b>). We next prepared cultures of neurons from 7-day-old-mice (<i>n </i>= 36). H<sub>2</sub>O<sub>2</sub> (10<sup>⁻5</sup> M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. PhSe)<sub>2</sub> was used as positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2’-nonenal, 8-isoprostane), DNA (8-hydroxy-2’-deoxyguanosine) and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, <b>3b</b>, <b>3d</b> and <b>3f</b> exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)<sub>2</sub>. These novel aromatic selenocyanates could be promising to be tried in most sophisticated <i>in vitro </i>studies or even at preclinical level.</p>

scholarly journals Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Tiago E. A. Frizon ◽  
José H. Cararo ◽  
Sumbal Saba ◽  
Gustavo C. Dal-Pont ◽  
Monique Michels ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Thiobarbituric Acid ◽  
Positive Control ◽  
Protein Carbonyl ◽  
Oxidative Challenge ◽  
Hydroxy Esters ◽  
Old Mice ◽  
Oxidative Stress Inducer

Herein, we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H2O2) in cultured mouse neurons. First, α-methylene-β-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (3a-f). We next prepared cultures of neurons from 7-day-old mice (n=36). H2O2 (10-5 M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. (PhSe)2 was used as a positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2′-nonenal, 8-isoprostane), DNA (8-hydroxy-2′-deoxyguanosine), and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, 3b, 3d, and 3f exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)2. These novel aromatic selenocyanates could be promising to be tried in most sophisticated in vitro studies or even at the preclinical level.

scholarly journals Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

2020 ◽  
Author(s):  
Tiago Elias Allievi Frizon ◽  
José H. Cararo ◽  
Sumbal Saba ◽  
Gustavo C. Dal-Pont ◽  
Monique Michels ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Thiobarbituric Acid ◽  
Positive Control ◽  
Protein Carbonyl ◽  
Oxidative Challenge ◽  
Hydroxy Esters ◽  
Old Mice ◽  
Oxidative Stress Inducer

<p>Herein we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in cultured mouse neurons. First, <i>α</i>-methylene-<i>β</i>-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (<b>3a-f</b>). We next prepared cultures of neurons from 7-day-old-mice (<i>n </i>= 36). H<sub>2</sub>O<sub>2</sub> (10<sup>⁻5</sup> M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. PhSe)<sub>2</sub> was used as positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2’-nonenal, 8-isoprostane), DNA (8-hydroxy-2’-deoxyguanosine) and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, <b>3b</b>, <b>3d</b> and <b>3f</b> exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)<sub>2</sub>. These novel aromatic selenocyanates could be promising to be tried in most sophisticated <i>in vitro </i>studies or even at preclinical level.</p>

scholarly journals TUALANG HONEY ATTENUATES KAINIC ACID-INDUCED OXIDATIVE STRESS IN RAT CEREBELLUM AND BRAINSTEM

2017 ◽  
Vol 9 (12) ◽  
pp. 155 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
K. N. S. Sirajudeen ◽  
Mustapha Muzaimi ◽  
Mummedy Swamy ◽  
Mohd Asnizam Asari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Total Antioxidant Status ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
Multiple Time ◽  
Rat Cerebellum ◽  
Total Antioxidant ◽  
Multiple Time Points ◽  
Tualang Honey

Objective: The present study examined the protective effect of tualang honey (TH) against kainic acid (KA)-induced oxidative stress in the cerebellum and brainstem of rats.Methods: Male Sprague-Dawley rats were randomly divided into four groups: Control, KA-treated, TH+KA-treated, and topiramate (TPM, an antiepileptic agent)+KA-treated groups. Rats were pretreated orally with drinking water, TH (1.0 g/kg body weight), or TPM (40 mg/kg body weight), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Oxidative stress markers were analyzed in different brain regions (cerebellum and brainstem) 2 h, 24 h, and 48 h after KA administration.Results: KA caused significant (p<0.05) elevation in the thiobarbituric acid reactive substances level, protein carbonyl contents, and nitric oxide production, impairment of glutathione system, and a significant reduction in the total antioxidant status in the rat cerebellum and brainstem at multiple time-points, as compared to control groups. Pretreatment with TH significantly (p<0.05) reduced the elevation in the thiobarbituric acid reactive substances level, protein carbonyl contents, and nitric oxide production and increasing a reduction in the total antioxidant status in the rat cerebellum and brainstem induced by KA at multiple time-points, as compared to KA only-treated group.Conclusion: Taken together, this study suggests that TH has therapeutic potential in reducing oxidative stress in the cerebellum and brainstem of KA-induced rats via its antioxidant property.

scholarly journals Hexarelin exerts neuroprotective and antioxidant effects against hydrogen peroxide-induced toxicity through the modulation of MAPK and PI3K/Akt patways in Neuro-2A cells

2020 ◽  
Author(s):  
Ramona Meanti ◽  
Laura Rizzi ◽  
Elena Bresciani ◽  
Laura Molteni ◽  
Vittorio Locatelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Apoptotic Cell ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Inhibitory Influence ◽  
No Production ◽  
Mrna Levels

AbstractHexarelin, a synthetic hexapeptide, protects cardiac and skeletal muscles by inhibiting apoptosis, both in vitro and in vivo. Moreover, evidence suggests that hexarelin could have important neuroprotective bioactivity.Oxidative stress and the generation of free radicals has been implicated in the etiologies of several neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and multiple sclerosis. In addition to direct oxidative stress, exogenous hydrogen peroxide (H2O2) can penetrate biological membranes and enhance the formation of other reactive oxygen species.The aim of this study was to examine the inhibitory influence of hexarelin on H2O2-induced apoptosis in Neuro-2A cells, a mouse neuroblastoma cell line. Our results indicate that H2O2 reduced the viability of Neuro-2A cells in a dose-related fashion. Furthermore, H2O2 induced significant changes in the morphology of Neuro-2A cells, reflected in the formation of apoptotic cell bodies, and an increase of nitric oxide (NO) production. Hexarelin effectively antagonized H2O2 oxidative damage to Neuro-2A cells as indicated by improved cell viability, normal morphology and reduced nitrite (NO2−) release. Hexarelin treatment of Neuro-2A cells also reduced mRNA levels of caspases−3 and −7 and those of the pro-apoptotic molecule Bax; by contrast, hexarelin treatment increased anti-apoptotic Bcl-2 mRNA levels. Hexarelin also reduced MAPKs phosphorylation induced by H2O2 and concurrently increased p-Akt protein expression.In conclusion, our results identify several neuroprotective and anti-apoptotic effects of hexarelin. These properties suggest that further investigation of hexarelin as a neuroprotective agent in an investigational and therapeutic context are merited.

scholarly journals Estimation of the Genotoxicityof Hydrogen Peroxide and Antioxidant Actionof Halo Acid by the Method of Dna-Cometwith the Use of the Model of Transplantable Cell Cultures

2018 ◽  
pp. 40-43
Author(s):  
Olga Verle ◽  
Oleg Ostrovskiy ◽  
Valerian Verovskiy ◽  
Galina Dudchenko
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
In Vitro Model ◽  
Cell Damage ◽  
Protective Action ◽  
Genetic Material ◽  
Optimal Level ◽  
Pharmacological Agents ◽  
Vitro Model

In the framework of the study, the degree of defragmentation of DNA by the DNA-comet method is evaluated when exposed to the cell culture of hydrogen peroxide (H2O2), and an in vitro model is developed to evaluate the antioxidant activity of new pharmacological agents. The results of working with cell lines show that the percentage of damage to the genetic material of cells of intact samples does not greatly vary from the method of removing the cellular monolayer from the culture plastic. Concerning the effect of H2O2 as an inducer of oxidative stress on DNA cell damage, the optimal level of DNA defragmentation has been modeled for subsequent studies of the protective action of antioxidants.

scholarly journals Redox Status in Women with Rheumathoid Arthritis

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Aleksandra Vranic ◽  
Aleksandra Antovic ◽  
Nevena Draginic ◽  
Marijana Andjic ◽  
Marko Ravic ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Cartilage Damage ◽  
Thiobarbituric Acid ◽  
Antioxidant Defense System ◽  
Redox Status ◽  
Female Population

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.

scholarly journals Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1366 ◽  
Author(s):  
Yoshiko Furukawa ◽  
Atsushi Sawamoto ◽  
Mizuki Yamaoka ◽  
Makiko Nakaya ◽  
Yuhzo Hieda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neurite Outgrowth ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Anti Oxidant ◽  
Neuro2a Cells ◽  
Cerebral Ischemic

Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.

scholarly journals Identification of Two Kinase Inhibitors with Synergistic Toxicity with Low-Dose Hydrogen Peroxide in Colorectal Cancer Cells In vitro

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122 ◽  
Author(s):  
Eric Freund ◽  
Kim-Rouven Liedtke ◽  
Lea Miebach ◽  
Kristian Wende ◽  
Amanda Heidecke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Hydrogen Peroxide ◽  
Protein Kinase ◽  
Tumor Cells ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Colorectal Cancer Cells

Colorectal carcinoma is among the most common types of cancers. With this disease, diffuse scattering in the abdominal area (peritoneal carcinosis) often occurs before diagnosis, making surgical removal of the entire malignant tissue impossible due to a large number of tumor nodules. Previous treatment options include radiation and its combination with intraperitoneal heat-induced chemotherapy (HIPEC). Both options have strong side effects and are often poor in therapeutic efficacy. Tumor cells often grow and proliferate dysregulated, with enzymes of the protein kinase family often playing a crucial role. The present study investigated whether a combination of protein kinase inhibitors and low-dose induction of oxidative stress (using hydrogen peroxide, H2O2) has an additive cytotoxic effect on murine, colorectal tumor cells (CT26). Protein kinase inhibitors from a library of 80 substances were used to investigate colorectal cancer cells for their activity, morphology, and immunogenicity (immunogenic cancer cell death, ICD) upon mono or combination. Toxic compounds identified in 2D cultures were confirmed in 3D cultures, and additive cytotoxicity was identified for the substances lavendustin A, GF109203X, and rapamycin. Toxicity was concomitant with cell cycle arrest, but except HMGB1, no increased expression of immunogenic markers was identified with the combination treatment. The results were validated for GF109203X and rapamycin but not lavendustin A in the 3D model of different colorectal (HT29, SW480) and pancreatic cancer cell lines (MiaPaca, Panc01). In conclusion, our in vitro data suggest that combining oxidative stress with chemotherapy would be conceivable to enhance antitumor efficacy in HIPEC.

scholarly journals Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress

2006 ◽  
Vol 25 (2) ◽  
pp. 242-249 ◽  
Author(s):  
Freddy J. Troost ◽  
Robert-Jan M. Brummer ◽  
Guido R. M. M. Haenen ◽  
Aalt Bast ◽  
Rachel I. van Haaften ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lipid Peroxidation ◽  
Small Intestine ◽  
Antioxidant Capacity ◽  
Intestinal Mucosa ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substances ◽  
Oxidative Challenge ◽  
Gene Reporters

Iron-induced oxidative stress in the small intestine may alter gene expression in the intestinal mucosa. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine. Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a randomized crossover design. After duodenal tissue sampling by gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a 40-cm segment of the proximal small intestine with saline and, subsequently, with either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion, a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, in intestinal fluid samples increased significantly and dose dependently at 30 min after the start of perfusion with 80 or 400 mg of iron, respectively ( P < 0.001). During the perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive substances was accompanied by a significant, momentary rise in trolox equivalent antioxidant capacity, an indicator of total antioxidant capacity ( P < 0.05). The expression of 89 gene reporters was significantly altered by both iron interventions. Functional mapping showed that both iron dosages mediated six distinct processes. Three of those processes involved G-protein receptor coupled pathways. The other processes were associated with cell cycle, complement activation, and calcium channels. Iron administration in the small intestine induced dose-dependent lipid peroxidation and a momentary antioxidant response in the lumen, mediated the expression of at least 89 individual gene reporters, and affected at least six biological processes.

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