scholarly journals Advantageous/Unfavorable Effect of Quercetin on the Membranes of SK-N-SH Neuroblastoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4945
Author(s):  
Barbara Kreczmer ◽  
Barbara Dyba ◽  
Anna Barbasz ◽  
Elżbieta Rudolphi-Szydło
Keyword(s):  
Cell Function ◽  
Antioxidant Properties ◽  
Neuroblastoma Cells ◽  
Chemical Properties ◽  
Redox Balance ◽  
Cytotoxic Action ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Unfavorable Effect ◽  
Antioxidative Action

Quercetin is a polyphenolic compound, the effects of which raise scientists’ doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).

scholarly journals Antioxidant and food additive BHA prevents TNF cytotoxicity by acting as a direct RIPK1 inhibitor

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Tom Delanghe ◽  
Jon Huyghe ◽  
Seungheon Lee ◽  
Dario Priem ◽  
Samya Van Coillie ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
In Silico Analysis ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Cellular Processes ◽  
Silico Analysis ◽  
Surprising Finding ◽  
Necrosis Factor ◽  
In Cells

AbstractButylate hydroxyanisole (BHA) is a synthetic phenol that is widely utilized as a preservative by the food and cosmetic industries. The antioxidant properties of BHA are also frequently used by scientists to claim the implication of reactive oxygen species (ROS) in various cellular processes, including cell death. We report on the surprising finding that BHA functions as a direct inhibitor of RIPK1, a major signaling hub downstream of several immune receptors. Our in silico analysis predicts binding of 3-BHA, but not 2-BHA, to RIPK1 in an inactive DLG-out/Glu-out conformation, similar to the binding of the type III inhibitor Nec-1s to RIPK1. This predicted superior inhibitory capacity of 3-BHA over 2-BHA was confirmed in cells and using in vitro kinase assays. We demonstrate that the reported protective effect of BHA against tumor necrosis factor (TNF)-induced necroptotic death does not originate from ROS scavenging but instead from direct RIPK1 enzymatic inhibition, a finding that most probably extends to other reported effects of BHA. Accordingly, we show that BHA not only protects cells against RIPK1-mediated necroptosis but also against RIPK1 kinase-dependent apoptosis. We found that BHA treatment completely inhibits basal and induced RIPK1 enzymatic activity in cells, monitored at the level of TNFR1 complex I under apoptotic conditions or in the cytosol under necroptosis. Finally, we show that oral administration of BHA protects mice from RIPK1 kinase-dependent lethality caused by TNF injection, a model of systemic inflammatory response syndrome. In conclusion, our results demonstrate that BHA can no longer be used as a strict antioxidant and that new functions of RIPK1 may emerge from previously reported effects of BHA.

Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity

2002 ◽  
Vol 21 (2) ◽  
pp. 71-75 ◽  
Author(s):  
K R Martin ◽  
J C Barrett
Keyword(s):  
Cell Signaling ◽  
Cellular Response ◽  
Redox Regulation ◽  
Cell Function ◽  
Redox Balance ◽  
Cell Number ◽  
Signaling Cascades ◽  
High Dose ◽  
Cellular Processes

ROS are diverse and abundant in biological systems. While excessive ROS production clearly damages DNA, low levels of ROS affect cell signaling particularly at the level of redox modulation. Moreover, the specific contributions of ROS to apoptosis and mitogenesis in maintenance of cell number homeostasis remains to be elucidated. ROS dose is a critical parameter in determining the ultimate cellular response; however the shape of the dose response curve is unpredictable. When cells are stimulated with ROS, cell-signaling cascades are activated. It appears that the cellular redox potential is an important determinant of cell function and interruption of redox balance may adversely affect cell function. As a result, compounds such as antioxidants may intercept critical ROS signaling molecules and both protect cells and foster pathogenesis. As a result, further study is needed to unravel the role of ROS in redox regulation and the potential outcome of antioxidant administration on cellular responses.

Amentoflavone: A Bifunctional Metal Chelator that Controls the Formation of Neurotoxic Soluble Aβ42 Oligomers

2020 ◽  
Author(s):  
Liang Sun ◽  
Anuj K. Sharma ◽  
Byung-Hee Han ◽  
Liviu M. Mirica
Keyword(s):  
Reactive Oxygen Species ◽  
Metal Ions ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Amyloid Plaques ◽  
Transition Metal Ions ◽  
Oxygen Species ◽  
High Affinity ◽  
Amyloid Aβ ◽  
Β Amyloid

<p>Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu<sup>2+</sup> with very high affinity (pCu<sub>7.4</sub> = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (<i>K<sub>i</sub></i> = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques <i>ex vivo</i> in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ<sub>42</sub> aggregation and disaggregation of Aβ<sub>42</sub> fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ<sub>42</sub> oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu<sup>2+</sup> and significantly diminish the Cu<sup>2+</sup>-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu<sup>2+</sup> and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD. </p>

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

scholarly journals Evaluation of Toxicity and Antioxidant Property of Cassia fistula Stem Bark Extracts in Zebrafish

2020 ◽  
Vol 10 (03) ◽  
pp. 109-115
Author(s):  
Shreya Udaya ◽  
Nishith Babu ◽  
Dechamma Pandyanda Nanjappa ◽  
Krithika Kalladka ◽  
Gunimala Chakraborty ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Antioxidant Property ◽  
Stem Bark ◽  
Oxygen Species ◽  
Cassia Fistula ◽  
Potential Applications ◽  
Ethanol Extracts ◽  
Stress Models

Abstract Objective This study was aimed at evaluating the toxicity and the antioxidant property of Cassia fistula stem bark extracts in zebrafish. Materials and Methods Crude aqueous and ethanol extracts of C. fistula stem bark were obtained following a standard solvent-based extraction method. The toxicity of these extracts on zebrafish embryonic development was determined and the LC50 values were calculated. Finally, the antioxidant property of C. fistula stem bark extracts was determined in arsenic-induced oxidative stress models of zebrafish. Results The aqueous extract of C. fistula stem bark showed a slightly larger LC50 value (213.6 ppm) compared with the ethanol extract (LC50 = 63.5 ppm), suggesting a lower toxicity of the aqueous extract. A significant reduction of reactive oxygen species (ROS) signal was observed in arsenic-exposed embryos treated with the aqueous extract, but not the ethanol extract, indicating that the antioxidant activity is present only in the aqueous extract of C. fistula stem bark. Conclusion Identification of antioxidants from natural sources is desirable because of increasing safety concerns associated with synthetic antioxidants. This study demonstrated that aqueous extract from C. fistula stem bark possesses antioxidant properties, which can be further characterized for mechanism of action and potential applications.

scholarly journals Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 329
Author(s):  
Daniel Chavarria ◽  
Ophelie Da Silva ◽  
Sofia Benfeito ◽  
Sandra Barreiro ◽  
Jorge Garrido ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Antioxidant Properties ◽  
Neuroblastoma Cells ◽  
Oxidation Potential ◽  
Fine Tuning ◽  
Mitochondrial Oxidative Stress ◽  
Electric Eel ◽  
Ic50 Values ◽  
System Extension ◽  
Inhibition Potency

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP+) conjugates (compounds 2–5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2–5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2–5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2–5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.

scholarly journals How to express the antioxidant properties of substances properly?

2021 ◽  
Author(s):  
Małgorzata Olszowy-Tomczyk
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Literature Review ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
The Body ◽  
Universal Method ◽  
Oxygen Species ◽  
Good Tool

AbstractOxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract

scholarly journals Novel Antioxidant Properties of Doxycycline

2018 ◽  
Vol 19 (12) ◽  
pp. 4078 ◽  
Author(s):  
Dahn Clemens ◽  
Michael Duryee ◽  
Cleofes Sarmiento ◽  
Andrew Chiou ◽  
Jacob McGowan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Chronic Inflammation ◽  
Antioxidant Properties ◽  
Antibacterial Properties ◽  
Reactive Oxygen ◽  
Protein Adducts ◽  
Oxygen Species ◽  
Free System

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.

scholarly journals Specific Modification of Aged Proteasomes Revealed by Tag-Exchangeable Knock-In Mice

2018 ◽  
Vol 39 (1) ◽  
Author(s):  
Takuya Tomita ◽  
Shoshiro Hirayama ◽  
Yasuyuki Sakurai ◽  
Yuki Ohte ◽  
Hidehito Yoshihara ◽  
...  
Keyword(s):  
Cell Function ◽  
Fluorescent Protein ◽  
Embryonic Fibroblasts ◽  
Α Subunit ◽  
Biochemical Alterations ◽  
Cellular Processes ◽  
Responsible Gene ◽  
Intracellular Protein Degradation ◽  
Green Fluorescent

ABSTRACT The proteasome is the proteolytic machinery at the center of regulated intracellular protein degradation and participates in various cellular processes. Maintaining the quality of the proteasome is therefore important for proper cell function. It is unclear, however, how proteasomes change over time and how aged proteasomes are disposed. Here, we show that the proteasome undergoes specific biochemical alterations as it ages. We generated Rpn11-Flag/enhanced green fluorescent protein (EGFP) tag-exchangeable knock-in mice and established a method for selective purification of old proteasomes in terms of their molecular age at the time after synthesis. The half-life of proteasomes in mouse embryonic fibroblasts isolated from these knock-in mice was about 16 h. Using this tool, we found increased association of Txnl1, Usp14, and actin with the proteasome and specific phosphorylation of Rpn3 at Ser 6 in 3-day-old proteasomes. We also identified CSNK2A2 encoding the catalytic α′ subunit of casein kinase II (CK2α′) as a responsible gene that regulates the phosphorylation and turnover of old proteasomes. These findings will provide a basis for understanding the mechanism of molecular aging of the proteasome.

scholarly journals The Antioxidant Role of Soy and Soy Foods in Human Health

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 635
Author(s):  
Gianluca Rizzo
Keyword(s):  
Clinical Trials ◽  
Scientific Evidence ◽  
Antioxidant Properties ◽  
Oxygen Species ◽  
Healthy Foods ◽  
Bioactive Substances ◽  
Soy Foods ◽  
Antioxidant Mechanisms ◽  
Final Synthesis

Oxidative stress seems to play a role in many chronic diseases, such as cardiovascular diseases, diabetes, and some cancers. Research is always looking for effective approaches in the prevention and treatment of these pathologies with safe strategies. Given the central role of nutrition, the identification of beneficial healthy foods can be the best key to having a safe and at the same time effective approach. Soy has always aroused great scientific interest but often this attention is galvanized by the interaction with estrogen receptors and related consequences on health. However, soy, soy foods, and soy bioactive substances seem to have antioxidant properties, suggesting their role in quenching reactive oxygen species, although it was frequently mentioned but not studied in depth. The purpose of this review is to summarize the scientific evidence of the antioxidant properties of soy by identifying the human clinical trials available in the literature. A total of 58 manuscripts were individuated through the literature search for the final synthesis. Soy bioactive substances involved in redox processes appear to be multiple and their use seems promising. Other larger clinical trials with adequate standardization and adequate choice of biomarkers will fill the gap currently existing on the suggestive role of soy in antioxidant mechanisms.

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