scholarly journals The toxic effect of Vu-Defr, a defensin from Vigna unguiculata seeds, on Leishmania amazonensis is associated with reactive oxygen species production, mitochondrial dysfunction, and plasma membrane perturbation

2018 ◽  
Vol 64 (7) ◽  
pp. 455-464 ◽  
Author(s):  
Géssika Silva Souza ◽  
Lais Pessanha de Carvalho ◽  
Edésio José Tenório de Melo ◽  
Valdirene Moreira Gomes ◽  
André de Oliveira Carvalho
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Membrane ◽  
Biological Activities ◽  
Reactive Oxygen ◽  
Leishmania Amazonensis ◽  
New Drugs ◽  
Oxygen Species ◽  
Membrane Perturbation ◽  
Plant Defensins

Plant defensins are plant antimicrobial peptides that present diverse biological activities in vitro, including the elimination of Leishmania amazonensis. Plant defensins are considered promising candidates for the development of new drugs. This protozoan genus has great epidemiological importance and the mechanism behind the protozoan death by defensins is unknown, thus, we chose L. amazonensis for this study. The aim of the work was to analyze the possible toxic mechanisms of Vu-Defr against L. amazonensis. For analyses, the antimicrobial assay was repeated as previously described, and after 24 h, an aliquot of the culture was tested for viability, membrane perturbation, mitochondrial membrane potential, reactive oxygen species (ROS) and nitric oxide (NO) inductions. The results of these analyses indicated that after interaction with L. amazonensis, the Vu-Defr causes elimination of promastigotes from culture, membrane perturbation, mitochondrial membrane collapse, and ROS induction. Our analysis demonstrated that NO is not produced after Vu-Defr and L. amazonensis interaction. In conclusion, our work strives to help to fill the gap relating to effects caused by plant defensins on protozoan and thus better understand the mechanism of action of this peptide against L. amazonensis.

scholarly journals In Vitro Inhibition of Streptococcus mutans Biofilm Formation on Hydroxyapatite by Subinhibitory Concentrations of Anthraquinones

2007 ◽  
Vol 51 (4) ◽  
pp. 1541-1544 ◽  
Author(s):  
Tom Coenye ◽  
Kris Honraet ◽  
Petra Rigole ◽  
Pol Nadal Jimenez ◽  
Hans J. Nelis
Keyword(s):  
Reactive Oxygen Species ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Membrane Perturbation ◽  
In Vitro Inhibition ◽  
Subinhibitory Concentrations

ABSTRACT We report that certain anthraquinones (AQs) reduce Streptococcus mutans biofilm formation on hydroxyapatite at concentrations below the MIC. Although AQs are known to generate reactive oxygen species, the latter do not underlie the observed effect. Our results suggest that AQs inhibit S. mutans biofilm formation by causing membrane perturbation.

Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method

Nanomedicine ◽  
2021 ◽  
Author(s):  
Tianyan Jiang ◽  
Haoxiang Guo ◽  
Ya-Nan Xia ◽  
Yun Liu ◽  
Dandan Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Copper Sulfide ◽  
Mitochondrial Membrane ◽  
3D Culture ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hepatocyte Spheroids

Aim: To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Materials & methods: Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. Results: The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity in vitro through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. Conclusion: We observed the hepatotoxicity of CuSNPs in vitro with associated mechanisms in an advanced 3D culture system.

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.

scholarly journals Antioxidant and Anticancer Activities and Protein Interaction of the Oxidovanadium(IV) Naringin Complex

Inorganics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 13
Author(s):  
Andrés Gonzalo Restrepo-Guerrero ◽  
Helen Goitia-Semenco ◽  
Luciana G. Naso ◽  
Marilin Rey ◽  
Pablo J. Gonzalez ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrophobic Interactions ◽  
Biological Activities ◽  
Physicochemical Characterization ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Synthetic Procedure

The complex of oxidovanadium(IV) with naringin (Narg) [VO(Narg)2] 8H2O (VONarg) was prepared according to the literature improving the synthetic procedure and physicochemical characterization. In addition, biological activities (cytotoxic, antioxidant, and BSA interaction) were determined. The metal coordinated through the 5-hydroxy and 4-carbonyl groups of rings A and C of naringin, respectively. The antioxidant activity of VONarg, determined in vitro, was higher than those of the flavonoid against superoxide and peroxyl reactive oxygen species (ROS) and DPPH radical. The cytotoxic properties were determined by a MTT assay on adenocarcinoma human alveolar basal epithelial cells (A549). VONarg exerted a 20% decrease in cancer cells viability at 24 h incubation, while naringin and oxidovanadium(IV) cation did not show cytotoxicity. Measurements with the normal HEK293 cell line showed that the inhibitory action of the complex is selective. VONarg generated intracellular reactive oxygen species (ROS), depletion of reduced glutathione and depolarization of mitochondrial membrane potential, typical for apoptotic pathway, producing cell death by oxidative stress mechanism. Moreover, naringin interacted with bovine serum albumin (BSA) through hydrophobic interactions in a spontaneous process, and VONarg showed greater affinity for the protein but can still be transported and delivered by it (Ka 104 L·mol−1 order).

scholarly journals Oxyresveratrol Possesses DNA Damaging Activity

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2577
Author(s):  
Sarayut Radapong ◽  
Satyajit D. Sarker ◽  
Kenneth J. Ritchie
Keyword(s):  
Reactive Oxygen Species ◽  
Biological Activities ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ability To Act ◽  
Phytochemical Profile ◽  
Dose Dependent ◽  
Anticancer Compound

Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their pro-oxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound.

NAC Improves the Differentiation of IPS Cells Into Hematopoietic Progenitors

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2349-2349
Author(s):  
Ina Berniakovich ◽  
Leopoldo Laricchia-Robbio ◽  
Juan Carlos Izpisua
Keyword(s):  
Reactive Oxygen Species ◽  
Stress Resistance ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Ips Cells ◽  
Oxygen Species ◽  
Cd34 Cells ◽  
Human Ips Cells

Abstract Abstract 2349 In vitro differentiation of human induced pluripotent stem (iPS) cells is a new way to obtain donor material for blood transplantation. However, this is a long process in the course of which cells are exposed to alien environmental factors, capable to change cellular properties and decrease cellular viability. Indeed, cells in vitro are exposed to mechanical stress, artificial growth surface, unnatural gas composition etc. This fact could partially explain why cells obtained during directed iPS cells differentiation have different qualities in comparison with the analogous population from in vivo. It is supposed that oxidative stress is the major underlying mechanism of negative influence of various in vitro environmental factors on cells. N-acetylcysteine (NAC) is a powerful antioxidant. Due to free radical scavenging ability, the principal function of NAC is rendered to the inhibition of cellular damage and cell death in response to reactive oxygen species. Cytoprotective function of NAC is well demonstrated both in vitro and in vivo. We have established a protocol to obtain hematopoietic stem cell-like cells from human iPS cells with a pick of their production at three weeks of differentiation. We analyzed how intracellular accumulation of reactive oxygen species and NO, as well as cell viability, apoptosis, stress resistance, mitochondrial membrane potential were changed during this process by comparing status of cultures at 1 and at 3 weeks of differentiation. We found that during differentiation cells progressively accumulated intracellular reactive oxygen species and increased production of NO. The level of apoptosis in culture was significantly higher at 3 weeks of differentiation than at 1 week. Cell viability, on the contrary, decreased from 1 week till 3 weeks of differentiation. Stress resistance quantified through the amount of cells resistant to the H2O2 treatment was also decreased in 3 weeks old cultures. We also demonstrated that during in vitro culture the mitochondrial membrane potential of the cells under basal conditions and upon stimulation with carbonyl cyanide m-chlorophenylhydrazone was decreased at 3 weeks of differentiation in comparison with that at 1 week. All these phenomena were reversed by NAC supplementation. Remarkably, NAC administration also improved the hematopoietic differentiation of human iPS cells in terms of production of CD34, CD45, CD43 positive cells, that showed normal functionality in colony forming unit assay. CD34+ cells obtained from NAC treated cultures also increased their migration towards SDF1, therefore showing an increased ability of our CD34+ cells to home into bone marrow. Our results suggest that supplementation with NAC is beneficial for the improvement of hematopoietic differentiation of human iPS cells. Disclosures: No relevant conflicts of interest to declare.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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