scholarly journals 2337

2017 ◽  
Vol 1 (S1) ◽  
pp. 7-7
Author(s):  
Trevi A. Mancilla ◽  
Gregory J. Aune
Keyword(s):  
Reactive Oxygen Species ◽  
Animal Models ◽  
Cardiac Fibroblasts ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Alternative Therapies ◽  
Cardiac Cells ◽  
Oxygen Species ◽  
Doxorubicin Cardiotoxicity

OBJECTIVES/SPECIFIC AIMS: Our research strives to understand the pathophysiology of doxorubicin cardiotoxicity, focusing on the understudied nonmyocyte cardiac cells. Our understanding will enable researchers to develop protective or alternative therapies for cancer patients and treatments for cancer survivors. METHODS/STUDY POPULATION: Early studies have been carried out in isolated primary cardiac fibroblasts. Cells were treated with varying doses of doxorubicin. Cell viability, proliferation, and reactive oxygen species generation have all been studied. Future studies will focus on mitochondrial assessment in treated cells and confirmation of findings in animal models. Potential therapies discovered in these studies will also be conducted in animal models. RESULTS/ANTICIPATED RESULTS: Our results show a direct effect of doxorubicin on cardiac fibroblasts in vitro. Treated cells show a decreased rate of proliferation and increased production of reactive oxygen species. Similarly to cardiomyocytes, we hypothesize that reactive oxygen species damage the mitochondria of cardiac fibroblasts thereby altering their function and playing a role in doxorubicin cardiotoxicity. DISCUSSION/SIGNIFICANCE OF IMPACT: Current therapies have not been able to adequately protect patients from the cardiotoxicity of doxorubicin and other anthracyclines. A complete understanding of how doxorubicin damages cardiac tissue will only be possible by studying all cell types of the heart. With a better understanding, alternative therapies can be developed to prevent or treat doxorubicin cardiotoxicity without sacrificing the efficacy of doxorubicin in treating cancer.

Novel Tetrazoles against Acanthamoeba castellanii Belonging to the T4 Genotype

Chemotherapy ◽  
2021 ◽  
Author(s):  
Yassmin Isse Wehelie ◽  
Naveed Ahmed Khan ◽  
Itrat Fatima ◽  
Areeba Anwar ◽  
Kanwal Kanwal ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Silver Nanoparticles ◽  
Reactive Oxygen Species Generation ◽  
Acanthamoeba Castellanii ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Species Determination ◽  
One Pot ◽  
Tetrazole Derivatives

Background: Acanthamoeba castellanii is a pathogenic free-living amoeba responsible for blinding keratitis and fatal granulomatous amoebic encephalitis. However, treatments are not standardized but can involve the use of amidines, biguanides, and azoles. Objectives: The aim of this study was to synthesize a variety of synthetic tetrazole derivatives and test their activities against A. castellanii. Methods: A series of novel tetrazole compounds were synthesized by one-pot method and characterized by NMR and mass spectroscopy. These compounds were subjected to amoebicidal, and cytotoxicity assays against A. castellanii belonging to the T4 genotype and human keratinocyte skin cells respectively. Additionally, reactive oxygen species determination and electron microscopy studies were carried out. Furthermore, two of the seven compounds were conjugated with silver nanoparticles to study their antiamoebic potential. Results: A series of seven tetrazole derivatives were synthesized successfully. The selected tetrazoles showed anti-amoebic activities at 10µM concentration against A. castellanii in vitro. The compounds tested caused increased reactive oxygen species generation in A castellanii, and significant morphological damage to amoebal membranes. Moreover, conjugation of silver nanoparticles enhanced antiamoebic effects of two tetrazoles. Conclusions: The results showed that azole compounds hold promise in the development of new formulations of anti-Acanthamoebic agents.

scholarly journals Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology

2020 ◽  
Vol 8 ◽  
Author(s):  
Elisa Carrasco ◽  
Juan Carlos Stockert ◽  
Ángeles Juarranz ◽  
Alfonso Blázquez-Castro
Keyword(s):  
Reactive Oxygen Species ◽  
Near Infrared ◽  
Chemical Reactivity ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Hot Electron ◽  
Redox Biology

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O2) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like per se chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to in situ ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments in vitro and in vivo will be presented, and tentative new avenues for further research will be advanced.

scholarly journals The H2S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2966 ◽  
Author(s):  
Milica Lazarević ◽  
Emanuela Mazzon ◽  
Miljana Momčilović ◽  
Maria Basile ◽  
Giuseppe Colletti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Microglial Cells ◽  
Oxygen Species ◽  
Bv2 Cells ◽  
The Central Nervous System

GYY4137 is a hydrogen sulfide (H2S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H2S donor, Na2S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.

LACK of IRON Binding by Pixantrone IS ASSOCIATED with Reduced PRODUCTION of Reactive Oxygen SPECIES and Myoctye Cytotoxicity IN VITRO.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4806-4806 ◽  
Author(s):  
Miles Hacker ◽  
Marc McKennon ◽  
Jack W. Singer
Keyword(s):  
Reactive Oxygen Species ◽  
Animal Models ◽  
Secondary Alcohol ◽  
Reactive Oxygen ◽  
New Drugs ◽  
Visible Range ◽  
Oxygen Species ◽  
Aliphatic Ketone ◽  
Structural Element

Abstract Abstract 4806 Introduction Pixantrone (PIX), an aza-anthracenedione, which has successfully completed a phase 3 trial (J Clin Oncol 2009; 27:15s, No. 8523) was designed to enhance clinical efficacy while significantly decreasing cardiotoxicity compared to doxorubicin (DOX) and mitoxantrone (MIT). Multidose administration, in animal models of equitoxic doses of PIX, MIT, and DOX, with or without prior therapy with DOX, resulted in minimal evidence for PIX cardiotoxicity compared with the severe histologic lesions seen with these other agents (Cavaletti et al: Investigational New Drugs 2007; 3:187-95). Both DOX and MIT contain a dihydroquinone structural element known to interact with iron. Additionally, DOX contains an aliphatic ketone which, once metabolized to the corresponding secondary alcohol metabolite doxorubicinol, is implicated in release of free iron and the chronic cardiotoxicity observed with DOX. In contrast, PIX has a nitrogen containing heterocycle which replaces the dihydroquinone, forming an aza-anthracenedione structure. PIX also does not contain an aliphatic ketone and cannot form metabolites analogous to doxorubicinol. Methods To validate the proposed mechanisms underlying the observed differences in cardiotoxicity, we used established spectrophotometric techniques to quantify iron:drug interactions that are thought to be mechanistic for chronic doxorubicin cardiotoxicity (Menna et al: Cardiovasc Toxicol 2007; 7:80–85). Results Adding increasing amounts of iron to drug solution, we observed that DOX and MIT underwent changes in visible range absorbance patterns, characteristic of drug:iron complex formation, confirming the expected 1:3 Fe(II)-drug ratio for both DOX and MIT. In contrast, no spectrophotometric changes were observed with iron added to PIX, clearly demonstrating that PIX does not bind iron. In vitro studies using H2C9 rat myocardial cells indicate that PIX (ID50 >50 μg/ml) is far less toxic than DOX (ID50= 1 μ/ml). Moreover, PIX does not induce significant reactive oxygen species (ROS) production in the H2C9 cells compared to DOX. Conclusion These results demonstrate that PIX does not bind iron and that its inability to bind iron and its reduced propensity to generate ROS may be the mechanism for reduced PIX cardiotoxicity in animal models compared to DOX or MIT. Disclosures: McKennon: Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment.

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