scholarly journals Nitroxide Radical-Containing Redox Nanoparticles Protect Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine Toxicity

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Monika Pichla ◽  
Łukasz Pulaski ◽  
Katarzyna Dominika Kania ◽  
Ireneusz Stefaniuk ◽  
Bogumił Cieniek ◽  
...  
Keyword(s):  
Protective Effect ◽  
Antioxidant Properties ◽  
Cellular Damage ◽  
Cellular Model ◽  
Mitochondrial Potential ◽  
Human Neuroblastoma ◽  
Mitochondrial Mass ◽  
Mitochondrial Superoxide ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) patients can benefit from antioxidant supplementation, and new efficient antioxidants are needed. The aim of this study was to evaluate the protective effect of selected nitroxide-containing redox nanoparticles (NRNPs) in a cellular model of PD. Antioxidant properties of NRNPs were studied in cell-free systems by protection of dihydrorhodamine 123 against oxidation by 3-morpholino-sydnonimine and protection of fluorescein against bleaching by 2,2-azobis(2-amidinopropane) hydrochloride and sodium hypochlorite. Model blood-brain barrier penetration was studied using hCMEC/D3 cells. Human neuroblastoma SH-SY5Y cells, exposed to 6-hydroxydopamine (6-OHDA), were used as an in vitro model of PD. Cells were preexposed to NRNPs or free nitroxides (TEMPO or 4-amino-TEMPO) for 2 h and treated with 6-OHDA for 1 h and 24 h. The reactive oxygen species (ROS) level was estimated with dihydroethidine 123 and Fluorimetric Mitochondrial Superoxide Activity Assay Kit. Glutathione level (GSH) was measured with ortho-phtalaldehyde, ATP by luminometry, changes in mitochondrial membrane potential with JC-1, and mitochondrial mass with 10-Nonyl-Acridine Orange. NRNP1, TEMPO, and 4-amino-TEMPO (25-150 μM) protected SH-SY5Y cells from 6-OHDA-induced viability loss; the protection was much higher for NRNP1 than for free nitroxides. NRNP1 were better antioxidants in vitro and permeated better the model BBB than free nitroxides. Exposure to 6-OHDA decreased the GSH level after 1 h and increased it considerably after 24 h (apparently a compensatory overresponse); NRNPs and free nitroxides prevented this increase. NRNP1 and free nitroxides prevented the decrease in ATP level after 1 h and increased it after 24 h. 6-OHDA increased the intracellular ROS level and mitochondrial superoxide level. Studied antioxidants mostly decreased ROS and superoxide levels. 6-OHDA decreased the mitochondrial potential and mitochondrial mass; both effects were prevented by NRNP1 and nitroxides. These results suggest that the mitochondria are the main site of 6-OHDA-induced cellular damage and demonstrate a protective effect of NRNP1 in a cellular model of PD.

scholarly journals pH-Responsive Redox Nanoparticles Protect SH-SY5Y Cells at Lowered pH in a Cellular Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 543
Author(s):  
Monika Pichla ◽  
Grzegorz Bartosz ◽  
Ireneusz Stefaniuk ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dependent Manner ◽  
Cellular Model ◽  
Ph Responsive ◽  
Mitochondrial Potential ◽  
Concentration Dependent Manner ◽  
Mitochondrial Mass ◽  
Promising Tool ◽  
6 Hydroxydopamine

The damage to SH-SY5Y cells by 6-hydroxydopamine (6-OHDA) is an established cellular model of Parkinson’s disease (PD). Redox nanoparticles are a promising tool for therapy, including neurodegenerative diseases. As pH of the brain tissue at sites affected by PD is lowered down to 6.5, we studied the effect of pH-responsive redox nanoparticles (poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]), which change their structure in a pH-dependent manner and become active below pH 7 (NRNPs pH), on the viability of SH-SY5Y cells treated with 6-OHDA at pH 6.5 and 7.4. Pretreatment of the cells with NRNPs pH (15–75 μM) prior to the 6-OHDA treatment increased their survival in a concentration-dependent manner at pH 6.5, but not at pH 7.4. Among several parameters studied (ATP and GSH content, the level of reactive oxygen species, mitochondrial potential, mitochondrial mass), only the mitochondrial mass was dose-dependently protected by NRNPs pH at pH 6.5, but not at pH 7.4. These results indicate that the action of NRNPs pH on mitochondria underlies their protective effect in this cellular model of PD. These results may have potential importance for future applications of NRNPs pH in preclinical and perhaps clinical studies.

scholarly journals Synthesis, Neuroprotection, and Antioxidant Activity of 1,1′-Biphenylnitrones as α-Phenyl-N-tert-butylnitrone Analogues in In Vitro Ischemia Models

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1127 ◽  
Author(s):  
Beatriz Chamorro ◽  
David García-Vieira ◽  
Daniel Diez-Iriepa ◽  
Estíbaliz Garagarza ◽  
Mourad Chioua ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Human Neuroblastoma ◽  
In Vitro Ischemia ◽  
Lipoxygenase Inhibition ◽  
Antioxidant Agent

Herein, we report the neuroprotective and antioxidant activity of 1,1′-biphenyl nitrones (BPNs) 1–5 as α-phenyl-N-tert-butylnitrone analogues prepared from commercially available [1,1′-biphenyl]-4-carbaldehyde and [1,1′-biphenyl]-4,4′-dicarbaldehyde. The neuroprotection of BPNs1-5 has been measured against oligomycin A/rotenone and in an oxygen–glucose deprivation in vitro ischemia model in human neuroblastoma SH-SY5Y cells. Our results indicate that BPNs 1–5 have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN), and they are quite similar to N-acetyl-L-cysteine (NAC), which is a well-known antioxidant agent. Among the nitrones studied, homo-bis-nitrone BPHBN5, bearing two N-tert-Bu radicals at the nitrone motif, has the best neuroprotective capacity (EC50 = 13.16 ± 1.65 and 25.5 ± 3.93 μM, against the reduction in metabolic activity induced by respiratory chain blockers and oxygen–glucose deprivation in an in vitro ischemia model, respectively) as well as anti-necrotic, anti-apoptotic, and antioxidant activities (EC50 = 11.2 ± 3.94 μM), which were measured by its capacity to reduce superoxide production in human neuroblastoma SH-SY5Y cell cultures, followed by mononitrone BPMN3, with one N-Bn radical, and BPMN2, with only one N-tert-Bu substituent. The antioxidant activity of BPNs1-5 has also been analyzed for their capacity to scavenge hydroxyl free radicals (82% at 100 μM), lipoxygenase inhibition, and the inhibition of lipid peroxidation (68% at 100 μM). Results showed that although the number of nitrone groups improves the neuroprotection profile of these BPNs, the final effect is also dependent on the substitutent that is being incorporated. Thus, BPNs bearing N-tert-Bu and N-Bn groups show better neuroprotective and antioxidant properties than those substituted with Me. All these results led us to propose homo-bis-nitrone BPHBN5 as the most balanced and interesting nitrone based on its neuroprotective capacity in different neuronal models of oxidative stress and in vitro ischemia as well as its antioxidant activity.

Insight into antioxidant properties of milk‐derived bioactive peptides in vitro and in a cellular model

2019 ◽  
Vol 25 (5) ◽  
pp. e3162 ◽  
Author(s):  
Federica Tonolo ◽  
Laura Moretto ◽  
Stefania Ferro ◽  
Alessandra Folda ◽  
Valeria Scalcon ◽  
...  
Keyword(s):  
Bioactive Peptides ◽  
Antioxidant Properties ◽  
Cellular Model ◽  
Insight Into

scholarly journals Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro

2019 ◽  
Vol 8 (4) ◽  
pp. 561 ◽  
Author(s):  
Angela Alamo ◽  
Rosita A. Condorelli ◽  
Laura M. Mongioì ◽  
Rossella Cannarella ◽  
Filippo Giacone ◽  
...  
Keyword(s):  
Protective Effect ◽  
Sperm Motility ◽  
Dose Response ◽  
Superoxide Anion ◽  
Male Fertility ◽  
Negative Impact ◽  
Sperm Parameters ◽  
Mitochondrial Superoxide ◽  
Chromatin Compactness

Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage.

scholarly journals Aqueous Extract of Cocoa Phenolic Compounds Protects Differentiated Neuroblastoma SH-SY5Y Cells from Oxidative Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1266
Author(s):  
Noelia Carballeda Sangiao ◽  
Susana Chamorro ◽  
Sonia de Pascual-Teresa ◽  
Luis Goya
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Phenolic Compounds ◽  
Protective Effect ◽  
Aqueous Extract ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Human Neuroblastoma ◽  
Antioxidant Defense Enzymes

Cocoa is a rich source of polyphenols, especially flavanols and procyanidin oligomers, with antioxidant properties, providing protection against oxidation and nitration. Cocoa phenolic compounds are usually extracted with methanol/ethanol solvents in order to obtain most of their bioactive compounds; however, aqueous extraction seems more representative of the physiological conditions. In this study, an aqueous extract of cocoa powder has been prepared and chemically characterized, and its potential protective effect against chemically-induced oxidative stress has been tested in differentiated human neuroblastoma SH-SY5Y cells. Neuronal-like cultured cells were pretreated with realistic concentrations of cocoa extract and its major monomeric flavanol component, epicatechin, and then submitted to oxidative stress induced by a potent pro-oxidant. After one hour, production of reactive oxygen species was evaluated by two different methods, flow cytometry and in situ fluorescence by a microplate reader. Simultaneously, reduced glutathione and antioxidant defense enzymes glutathione peroxidase and glutathione reductase were determined and the results used for a comparative analysis of both ROS (reactive oxygen species) methods and to test the chemo-protective effect of the bioactive products on neuronal-like cells. The results of this approach, never tested before, validate both analysis of ROS and indicate that concentrations of an aqueous extract of cocoa phenolics and epicatechin within a physiological range confer a significant protection against oxidative insult to neuronal-like cells in culture.

scholarly journals Viburnum opulus L. Fruit Extracts Protect Human Neuroblastoma SH-SY5Y Cells against Hydrogen Peroxide-Induced Cytotoxicity

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 5 ◽  
Author(s):  
Paşayeva ◽  
Arslan ◽  
Kararenk
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Biological Activities ◽  
Iridoid Glycosides ◽  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Anticancer Activities ◽  
Viburnum Opulus ◽  
Human Neuroblastoma

Viburnum L., is one of the most diverse genera of Caprifoliaceae family. There are 4 species of this genus in Turkey. One of them is Viburnum opulus L. The fruits of V. opulus have been used as an antidiabetic in Turkish folk medicine and a traditional drink named “gilaburu” in Middle Anatolia. Oxidative stress is involved in the cell degenerative changes in the pathogenesis of a wide variety of human chronic diseases, such as cancer. Some of the studies carried out on the V. opulus extracts revealed the presence of phenolic acids, flavonoids, hydroxybenzoic acids, tannins, coumarins, cathechols, iridoid glycosides, antocyanins, and some others. Most of these polyphenols have various biological activities, including antioxidant, cancer chemopreventive, and anticancer activities. This study aimed to assess the in vitro antioxidant properties of the ethanol extract (VOE), decoction (VOD) and fruit juice (VOFJ) from the fruits of V. opulus against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study revealed that the VOE, VOD and VOFJ provided neuroprotection against H2O2-induced oxidative stress. In conclusion, VOE, VOD and VOFJ can be used as a functional dietary ingredient that might help in reducing health problems associated with various oxidative stress insults.

scholarly journals Antioxidant Properties and Protective Effect of Aqueous Anti-Ulcer Drug (AQAUD) against Aspirin-induced Gastric Ulcers in Albino Rats

2020 ◽  
pp. 9-21
Author(s):  
B. A. Mba ◽  
C. S. Alisi ◽  
A. C. Ene
Keyword(s):  
Protective Effect ◽  
Antioxidant Properties ◽  
Toxicity Testing ◽  
Antioxidant Potential ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Protective Effects ◽  
Sod Activity ◽  
Group I

Aim: The aim of this study is to evaluate the antioxidant properties and protective effects of aqueous anti-ulcer drug (AQAUD) against aspirin-induced gastric ulcer in albino rats. Methods: In this study, 30 male albino rats were divided into 5 groups of 6 each. Rats in group I served as normal control and received food and water. Animals in group II received food and water in addition to aspirin (400 mg/kg.b.wt) orally on the 14th day. Rats in groups III, IV and V received “AQAUD” (250 mg/kg.b.wt), (500 mg/kg.b.wt) and Omeprazole (20 mg/kg.b.wt) respectively for 14 days and aspirin (400 mg/kg.b.wt) orally on the 14th day. In vitro antioxidant property of “AQAUD” was assessed by its nitric oxide and hydroxyl radicals scavenging properties. The ulcer protective effect of “AQAUD” was assessed by determining the free and total acidity, ulcer index and % protection in the stomach content. The antioxidant potential in animals was evaluated by determining the concentrations of malondialdehyde and reduced glutathione. Superoxide dismutase and catalase activities were assayed in the stomach homogenates to further assess antioxidant potential. Total phenolics and flavonoid compounds were quantified to know the antioxidant content. Histopathological assessment of the gastric mucosa was used to assess the protective potentials of “AQAUD”. Data were analyzed using Statistical Package for Social Science (SPSS) version 21. Results: The results revealed that free acidity and ulcer indexes were significantly (p<0.05) reduced by “AQAUD”. There was a significant decrease in SOD activity of the stomach homogenates when compared to the aspirin group, with values for “AQAUD” 250 mg/kg.b.wt and “AQAUD” 500 mg/kg b.wt as 37.24±5.39ux10-2/mg protein and 23.64±2.91ux10-2/mg protein respectively. Result of acute toxicity testing showed that “AQAUD” is generally safe up to 5000 mg/kg b.wt. Conclusion: The results revealed that treatment with aspirin caused loss of gland architecture with erosion of epithelial layer, but AQAUD treatment ameliorated the effect of aspirin administration. The study revealed that “AQAUD” has considerable antioxidant potentials and can effectively protect against gastric ulcers.

Methylseleninic Acid (MSA) Decreases DNA Synthesis, Induces Cell Death, and Sensitizes Both Rituximab Sensitive and Rituximab-Resistant Non-Hodgkin’s Lymphoma Cell Lines to the Anti-Tumor Activity of Cisplatin and Gemcitabine.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4517-4517
Author(s):  
Francisco J. Hernandez-Ilizaliturri ◽  
Minhas Ali ◽  
Joy Knight ◽  
Youcef M. Rustum ◽  
Myron S. Czuczman
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
B Cell ◽  
Cell Lines ◽  
Drug Exposure ◽  
Antioxidant Properties ◽  
B Cell Lymphoma ◽  
Mitochondrial Potential ◽  
Salvage Regimen

Abstract Selenium (Se) is an essential trace element with antioxidant properties. Examination of the dietary intake of Se in more than 25 countries found an inverse correlation with total age-adjusted cancer mortality. In addition, other investigator had shown that low serum levels of Se correlate with an adverse outcome in patients with diffuse large B-cell lymphoma (DLBCL) undergoing anthracycline-base chemotherapy. Various Se compounds had been developed and are undergoing preclinical testing such as MSA or Sodium selenite (SS). SS has been shown to decrease PKCg activity and induce apoptosis in murine lymphomas. In an attempt to further evaluate the role of Se in human lymphomas we studied the effects of MSA in a panel of rituximab-sensitive (RSCL) and rituximab-resistant cell lines (RRCL). Resistant clones were generated by chronic exposure of Raji, RL or DHL-4 cells to escalating doses of rituximab with (4RH) or without (2R) human complement. Functional assays were performed to demonstrate decrease in rituximab sensitivity on RRCL. In addition, resistance to chemotherapy (CDDP, doxorubicin, vincristine, etc.) agents was demonstrated in RRCL. Lymphoma cells were exposed in vitro to MSA (0 to 5mM) with or without CDDP (0 to 10mM) or gemcitabine (0 to 10mM). Following a 72 hour-period of MSA-drug exposure, changes in mitochondrial potential were determined by alamar blue reduction measured at 30 minutes intervals over a 48 hr period. In addition, changes in DNA synthesis and cell proliferation following drug exposure were performed using standard [3H]-thymidine incorporation assays. MSA induced dose-dependent cell death and a decrease in DNA synthesis in all the cell lines tested (both RSCL and RRCL). Up to a 50% reduction in mitochondrial potential and cell viability was observed in RRCL or RSCL exposed to 5mM of MSA. Incubation of RSCL and RRCL to 5mM of MSA induced synergistic cytotoxic and anti-proliferative effects when combined with CDDP or gemcitabine. Our data demonstrates that MSA is active against various RSCL and RRCL and potentiates the anti-tumor effects of chemotherapy agents. Our findings strongly suggest that MSA added to systemic chemotherapy (i.e. combination of gemcitabine and cisplatin) may result in a novel and potent salvage regimen against relapsed/refractory B-cell lymphomas.

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