Effect of Diquat on the Antioxidant System and Cell Growth in Human Neuroblastoma Cells

Slaughter, M. R.; Thakkar, Hemangini; O’Brien, Peter J.

doi:10.1006/taap.2001.9322

Cited by 30 publications

(20 citation statements)

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“…Diquat does not bind covalently with biological molecules, but it stimulates cellular production of ROS by undergoing cyclic reduction-oxidation processes. It has been -E-mail: daiwenc@yahoo.com widely used as an effective chemical agent for the induction of oxidative stress (Slaughter et al, 2002;Osburn et al, 2006). Fu et al (1999) used oxidative stress induced by an intraperitoneal injection of 24 mg/kg BW to determine the protection of cellular glutathione peroxidase-1.…”

Section: Introductionmentioning

confidence: 99%

Responses of growth performance and tryptophan metabolism to oxidative stress induced by diquat in weaned pigs

Mao

et al. 2012

Animal

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During many pathological conditions, the tryptophan concentration in blood may be reduced. However, the effects of oxidative stress on tryptophan metabolism remain unknown. In this study, we investigated the effects of oxidative stress on growth performance and tryptophan metabolism in weaned pigs. A total of 24 weaned pigs were assigned to one of three treatments that included pigs fed ad libitum (control), pigs challenged with diquat at a dose of 10 mg/kg BW and fed ad libitum (oxidative stress) or pigs pair-fed to receive the same amount of feed as the diquat-challenged pigs. The trial lasted for 7 days. The growth performance and activities of antioxidant enzymes were declined in diquat-challenged pigs. The diquat challenge decreased the tryptophan concentration in serum and the 5-hydroxytryptamine concentration in the hypothalamus, and increased large neutral amino acids, kynurenine (Kyn) and malondialdehyde in serum. The 544-bp porcine partial mRNA sequence of the tryptophan 2,3-dioxygenase (TDO) gene was obtained according to the conserved region in the human gene sequence. In addition, the oxidative stress induced by the diquat challenge stimulated TDO-relative mRNA abundance in the liver and g-glutamyl transpeptidase activity in intestinal mucosa, but did not affect the mRNA levels of Na 1 -neutral amino acid transporter B0. These results suggested that oxidative stress induced by diquat depressed growth performance and increased metabolism of tryptophan via Kyn pathway that upregulated TDO mRNA expression in weaned pigs.

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Section: Introductionmentioning

confidence: 99%

Responses of growth performance and tryptophan metabolism to oxidative stress induced by diquat in weaned pigs

Mao

et al. 2012

Animal

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“…HCA imaging enables the full diversity and asynchronicity of individual cellular changes to be seen, which are typically summated in conventional population-based assays. For example, proliferation can be decreased overall, but some cells can also undergo an adaptive increase in a signal, thereby cancelling out a decrease in another cell because of its loss of viability [32]. A second advantage of HCA is multiparametric monitoring.…”

Section: The Hca Track Record In Drug Discoverymentioning

confidence: 99%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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“…The basis for the hormesis is thought to be multifactorial depending on the drug. It may be attributable to a compensatory adaptive response to chemical stress that is overwhelmed as the stress progresses; this has shown to be the case, for example, with diquat [11] and may well be the case for Mz and AC. The anthracyclines are known to produce anticancer effects by their intercalation into DNA to inhibit the cell cycle [12].…”

Section: In Vitro Drug Effectsmentioning

confidence: 99%

Application of High‐Content Analysis in Clinical Cytology for Translational Safety Biomarkers of Drug‐Induced Toxicity for Lymphoma Chemotherapy

Domingos

Davies

O’Brien

2014

Basic Clin Pharma Tox

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Drug cytotoxicity detected by high-content analysis (HCA) of live, cultured, human hepatocytes concurs with human toxic potential. We assessed HCA effectiveness in vivo using human, lymphoma line (HuT-78) and blood cells from healthy dogs and lymphomatous dogs treated with anticancer drugs: cytarabine, arsenic trioxide (AT), doxorubicin and mitoxantrone. DNA was stained with Hoechst-33342, calcium with fluo-4, mitochondria with TMRM and cell permeability with toto-3. HuT-78 and canine blood lymphocytes were treated 24 hr with 10 times increasing drug concentrations to determine concentrationresponse relationships to test agents. These showed hormesis (biphasic response) for TMRM and nuclear area. Fluorescence intensity was decreased with AT and mitoantrone but increased with cytarabine for TMRM, decreased from cell injury or anthracycline interaction for Hoechst-33342 and decreased with AT and interfered with by doxorubicin for fluo-4. Nuclear area increased with anthracyclines and AT. Mitochondria, calcium and nuclear area were affected in peripheral blood lymphocytes of lymphomatous dogs receiving chemotherapy: mitochondria were inhibited by acute treatment, but increased 2 weeks after treatment, as were ionized calcium, nuclear area and DNA. We conclude (i) concentration-response relationships are determinable in vitro for human and canine lymphocytes by HCA, (ii) cytotoxicity is detectable in vivo during and after anticancer drug treatment using canine blood lymphocytes: mitochondria are most affected, with smaller changes in calcium and nuclei and (iii) blood cell viability may be a biomarker for anticancer drug toxicity.

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Effect of Diquat on the Antioxidant System and Cell Growth in Human Neuroblastoma Cells

Cited by 30 publications

References 50 publications

Responses of growth performance and tryptophan metabolism to oxidative stress induced by diquat in weaned pigs

Responses of growth performance and tryptophan metabolism to oxidative stress induced by diquat in weaned pigs

High-content analysis for drug delivery and nanoparticle applications

Application of High‐Content Analysis in Clinical Cytology for Translational Safety Biomarkers of Drug‐Induced Toxicity for Lymphoma Chemotherapy

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