492 results match your criteria Toxicity Disulfiram


Higher sensitivity of female cells to ethanol: methylation of DNA lowers Cyp2e1, generating more ROS.

Cell Commun Signal 2020 Jul 11;18(1):111. Epub 2020 Jul 11.

Queens College and Graduate Center, City University of New York, 65-30 Kissena Blvd, NSB E143, Flushing, NY, 11367, USA.

Background: Cells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol.

Methods: We evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states. Read More

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http://dx.doi.org/10.1186/s12964-020-00616-8DOI Listing

Cancer Pro-oxidant Therapy Through Copper Redox Cycling: Repurposing Disulfiram and Tetrathiomolybdate.

Authors:
Manuel Rieber

Curr Pharm Des 2020 Jun 27. Epub 2020 Jun 27.

IVIC, Cancer Cell Biology Laboratory, CMBC, Caracas 1020A. Venezuela.

Background: Copper (Cu) is a transition metal active in Fenton redox cycling from reduced Cu+ and H2O2, to oxidized Cu2+ and the hydroxyl radical (∙OH) highly reactive oxygen species (ROS). At homeostatic Cu levels, ROS promote cell proliferation, migration, angiogenesis, and wound repair. To limit ROS toxicity, cells use Cu-dependent chaperone proteins, Cu-binding ceruloplasmin, and Cu-modulated enzymes like superoxide dismutases (SOD) like SOD1 and SOD3 to scavenge excess superoxide anion which favours Cu+ reduction, and mitochondrial cytochrome c oxidase, important in aerobic energy production. Read More

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http://dx.doi.org/10.2174/1381612826666200628022113DOI Listing

4-hydroxy-2-nonenal decreases coronary endothelial cell migration: Potentiation by aldehyde dehydrogenase 2 inhibition.

Vascul Pharmacol 2020 Jun 22:106762. Epub 2020 Jun 22.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, United States of America; Department of Physiology, Wayne State University, Detroit, MI 48202, United States of America. Electronic address:

4-hydroxynonenal (4HNE) is a reactive aldehyde, which is involved in oxidative stress associated pathogenesis. The cellular toxicity of 4HNE is mitigated by aldehyde dehydrogenase (ALDH) 2. Thus, we hypothesize that ALDH2 inhibition exacerbates 4HNE-induced decrease in coronary endothelial cell (EC) migration in vitro. Read More

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http://dx.doi.org/10.1016/j.vph.2020.106762DOI Listing
June 2020
4.620 Impact Factor

Acute Disulfiram Poisoning in a Child: A Case Report and Review of Literature.

Indian J Crit Care Med 2020 Mar;24(3):203-205

Department of Pharmacology, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India.

Aim: To determine the significance of acute disulfiram poisoning in pediatric population.

Background: Disulfiram poisoning in children is uncommon, can occur in children who have ingested large amount of drug because of careless and unsafe storage. Only few cases have been reported in literature. Read More

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http://dx.doi.org/10.5005/jp-journals-10071-23371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225768PMC

Developing New Cancer Nanomedicines by Repurposing Old Drugs.

Angew Chem Int Ed Engl 2020 Apr 8. Epub 2020 Apr 8.

Shanghai Institute of Ceramics, Chinese Academy of Sciences, State Key Laboratory of High Performance Ceramics and Superfine Microstructure, 1295 Ding-Xi Road, 200050, Shanghai, CHINA.

The high morbidity and mortality of cancer urge for innovative therapeutics. Very recently, several old drugs approved by US Food and Drug Administration (FDA) or undergoing clinical trials, such as 2-deoxy-D-glucose, disulfiram, artemisinin, chloroquine, metformin and aspirin, which have been extensively applied clinically for the treatments of other diseases with reliable evidences of biosafety, have been engineered into nanosystems for enhancing cancer therapy. These old drugs can cooperate with other components of nanosystems or the ambient biological environments, to favor tumor-specific therapeutics by nontoxicity-to-toxicity transition. Read More

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http://dx.doi.org/10.1002/anie.202004317DOI Listing

Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.

Bioorg Med Chem Lett 2020 Jun 28;30(11):127148. Epub 2020 Mar 28.

Department of Chemistry, Duke University, Durham, NC 27708-0354 USA. Electronic address:

Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Read More

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http://dx.doi.org/10.1016/j.bmcl.2020.127148DOI Listing

A CD44-targeted Cu(ii) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer.

Nanoscale 2020 Apr 1;12(15):8139-8146. Epub 2020 Apr 1.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China.

Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Read More

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http://dx.doi.org/10.1039/d0nr00434kDOI Listing

Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper.

Free Radic Biol Med 2020 Apr 4;150:1-11. Epub 2020 Feb 4.

Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. Electronic address:

Therapies for lung cancer patients initially elicit desirable responses, but the presence of hypoxia and drug resistant cells within tumors ultimately lead to treatment failure. Disulfiram (DSF) is an FDA approved, copper chelating agent that can target oxidative metabolic frailties in cancer vs. normal cells and be repurposed as an adjuvant to cancer therapy. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2020.01.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299833PMC

Aldehyde dehydrogenase 2 inhibition potentiates 4-hydroxy-2-nonenal induced decrease in angiogenesis of coronary endothelial cells.

Cell Biochem Funct 2020 Apr 13;38(3):290-299. Epub 2020 Jan 13.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan.

Coronary endothelial cell (EC) dysfunction including defective angiogenesis is reported in cardiac diseases. 4-Hydroxynonenal (4HNE) is a lipid peroxidation product, which is increased in cardiac diseases and implicated in cellular toxicity. Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that metabolizes 4HNE and reduces 4HNE-mediated cytotoxicity. Read More

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http://dx.doi.org/10.1002/cbf.3468DOI Listing
April 2020
2.005 Impact Factor

Vitamin B Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells.

Biomolecules 2020 Jan 1;10(1). Epub 2020 Jan 1.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region 142290, Russia.

We have shown that hydroxycobalamin (vitamin В) increases the toxicity of diethyldithiocarbamate (DDC) to tumor cells by catalyzing the formation of disulfiram (DSF) oxi-derivatives. The purpose of this study was to elucidate the mechanism of tumor cell death induced by the combination DDC + В. It was found that cell death induced by DDC + B differed from apoptosis, autophagy, and necrosis. Read More

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http://dx.doi.org/10.3390/biom10010069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023477PMC
January 2020

Fomepizole to treat disulfiram-ethanol reaction: a case series.

Clin Toxicol (Phila) 2019 Dec 26:1-4. Epub 2019 Dec 26.

Department of Medical and Toxicological Critical Care, Federation of Toxicology APHP, Lariboisière Hospital, University of Paris, Paris, France.

Disulfiram-ethanol reaction (DER) due to acetaldehyde accumulation occurs after drinking ethanol during disulfiram therapy. DER may result in life-threatening toxicity requiring urgent critical care. Fomepizole, an alcohol dehydrogenase inhibitor used to treat toxic alcohol poisoning, has been suggested for treating DER by preventing the metabolism of ethanol to acetaldehyde. Read More

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http://dx.doi.org/10.1080/15563650.2019.1708091DOI Listing
December 2019

Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions.

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Division of Infectious Diseases, Veterans Affairs Western New York Healthcare System, Buffalo, New York, USA.

Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. Read More

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http://dx.doi.org/10.1128/AAC.02167-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038249PMC
February 2020

Comparative effects of Mancozeb and Disulfiram-induced striated muscle myopathies in Long-Evans rats.

Environ Toxicol Pharmacol 2020 Feb 16;74:103300. Epub 2019 Nov 16.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA. Electronic address:

Dithiocarbamates (DTCs) like mancozeb (MZ) and disulfiram (DS) are used throughout agriculture and medicine and have been implicated in neurotoxicity. Little research has been studied on the reported myopathies caused by these compounds. Their pathogenesis and mechanism of muscle toxicity has not been fully studied. Read More

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http://dx.doi.org/10.1016/j.etap.2019.103300DOI Listing
February 2020

A dithiocarbamate-based HO-responsive prodrug for combinational chemotherapy and oxidative stress amplification therapy.

Chem Commun (Camb) 2019 Nov;55(92):13896-13899

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

Here, we report the rational design of a H2O2-responsive diethyldithiocarbamate (DTC)-based prodrug, which chelated Cu(ii) to form Cu(DTC)2 with a high anticancer activity in a tumor-microenvironment and induced oxidative stress amplification, showing superior antitumor toxicity to disulfiram. Read More

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http://dx.doi.org/10.1039/c9cc05438cDOI Listing
November 2019
1 Read

The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1.

Int J Mol Sci 2019 Oct 22;20(20). Epub 2019 Oct 22.

Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Read More

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http://dx.doi.org/10.3390/ijms20205225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834119PMC
October 2019

Mental retardation in Down syndrome: Two ways to treat.

Authors:
Pierre P Kamoun

Med Hypotheses 2019 Oct 26;131:109289. Epub 2019 Jun 26.

Biochemistry and Molecular Biology, Paris-Descartes University, 26 rue de Chartres, 92200 Neuilly, France. Electronic address:

Mental retardation is a progressive condition in Down syndrome: intelligence starts to decline linearly within the first year. This phenomenon could be related to the overproduction of a toxic compound, hydrogen sulfide. Indeed, a gene located on chromosome 21 controls the production of cystathionine-β-synthase, an enzyme involved in hydrogen sulfide production in the central nervous system. Read More

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http://dx.doi.org/10.1016/j.mehy.2019.109289DOI Listing
October 2019
3 Reads

Differential Susceptibility of and Species to Compound-Enhanced Copper Toxicity.

Front Microbiol 2019 30;10:1720. Epub 2019 Jul 30.

Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, United States.

Rationale: Mycoplasmas represent important etiologic agents of many human diseases. Due to increasing antimicrobial resistance and slow rate of novel discovery, unconventional methods of drug discovery are necessary. Copper ions are utilized in host microbial killing, and bacteria must regulate intracellular Cu concentrations to avoid toxicity. Read More

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http://dx.doi.org/10.3389/fmicb.2019.01720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682632PMC
July 2019
5 Reads

Disulfiram facilitates ataxin-3 nuclear translocation and potentiates the cytotoxicity in a cell model of SCA3.

Authors:
Zijian Wang

J Toxicol Sci 2019 ;44(8):535-542

Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, China.

Spinocerebellar ataxia type 3 (SCA3) is caused by the expansion of a glutamine-encoding CAG repeat in the ATXN3 gene encoding the protein ataxin-3. The nuclear presence of polyglutamine-expanded ataxin-3 is of critical importance for the pathogenesis of SCA3. Disulfiram, an FDA-approved drug for alcoholism, has also garnered attention in cancer treatment. Read More

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http://dx.doi.org/10.2131/jts.44.535DOI Listing
December 2019
4 Reads

Enhanced Tumor-Specific Disulfiram Chemotherapy by Cu Chelation-Initiated Nontoxicity-to-Toxicity Transition.

J Am Chem Soc 2019 07 15;141(29):11531-11539. Epub 2019 Jul 15.

The State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050 , People's Republic of China.

The antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of "alcohol-dependence", is Cu-dependent, but the intrinsic anfractuous biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its application. Herein, we report an Cu chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific "nontoxicity-to-toxicity" transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu-doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu ions induced by the mild acidic conditions of the tumor microenvironment. Read More

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http://dx.doi.org/10.1021/jacs.9b03503DOI Listing
July 2019
16 Reads

Process of immunogenic cell death caused by disulfiram as the anti-colorectal cancer candidate.

Biochem Biophys Res Commun 2019 06 16;513(4):891-897. Epub 2019 Apr 16.

Department of Immunology, School of Life Sciences and Biopharmaceuticals Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Guangdong Engineering & Technology Research Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Key Laboratory of Digital Quality Evaluation of Chinese Medical of State Administration of TCM, Guangzhou, 510006, PR China. Electronic address:

Background: Disulfiram (DSF), a drug widely used to control alcoholism, which has anticancer activity by inducing apoptosis in a copper (Cu)-dependent manner. Numerous evidences from mouse experiments indicated that some anti-cancer agents of chemotherapeutic drugs favor the induction of immunogenic cancer cell death (ICD) leading to tumor-specific immune responses. However, whether DSF could induce the colorectal tumor cells death and the mechanism involved in ICD regulatory remains elusive. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.03.192DOI Listing
June 2019
27 Reads

Anticancer response to disulfiram may be enhanced by co-treatment with MEK inhibitor or oxaliplatin: modulation by tetrathiomolybdate, KRAS/BRAF mutations and c-MYC/p53 status.

Ecancermedicalscience 2019 8;13:890. Epub 2019 Jan 8.

Instituto Venezolano de Investigaciones Cientificas, Tumor Cell Biology Laboratory, Caracas 1020-A, Venezuela.

Ammonium tetrathiomolybdate (TTM) and disulfiram (DSF) are copper (Cu) chelators in cancer clinical trials partly because Cu chelation: a) restricts the activity of Cu-binding MEK1/2 enzymes which drive tumourigenesis by KRAS or BRAF oncogenic mutations and b) enhances uptake of oxaliplatin (OxPt), clinically used in advanced KRAS-mutant colorectal carcinomas (CRC). Whereas TTM decreases intracellular Cu trafficking, DSF can reach other Cu-dependent intracellular proteins. Since the use of individual or combined Cu chelation may help or interfere with anti-cancer therapy, this study investigated whether TTM modifies the response to DSF supplemented with: 1) UO126, a known MEK1/2 inhibitor; 2) other Cu chelators like neocuproine (NC) or 1, 10-o-phenanthroline (OPT) in wt p53 melanoma cells differing in BRAF or KRAS mutations; 3) OxPt in mutant p53 CRC cells devoid of KRAS and BRAF mutations or harbouring either KRAS or BRAF mutations. Read More

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http://dx.doi.org/10.3332/ecancer.2019.890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369974PMC
January 2019
13 Reads

A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma.

J Neurooncol 2019 May 15;142(3):537-544. Epub 2019 Feb 15.

Washington University School of Medicine, St. Louis, MO, USA.

Purpose: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. Read More

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http://dx.doi.org/10.1007/s11060-019-03125-yDOI Listing
May 2019
18 Reads

Targeting genotoxic and proteotoxic stress-response pathways in human prostate cancer by clinically available PARP inhibitors, vorinostat and disulfiram.

Prostate 2019 03 29;79(4):352-362. Epub 2018 Nov 29.

Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Background: Castration-resistant prostate cancer (PCa) represents a serious health challenge. Based on mechanistically-supported rationale we explored new therapeutic options based on clinically available drugs with anticancer effects, including inhibitors of PARP1 enzyme (PARPi), and histone deacetylases (vorinostat), respectively, and disulfiram (DSF, known as alcohol-abuse drug Antabuse) and its copper-chelating metabolite CuET that inhibit protein turnover.

Methods: Drugs and their combination with ionizing radiation (IR) were tested in various cytotoxicity assays in three human PCa cell lines including radio-resistant stem-cell like derived cells. Read More

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http://dx.doi.org/10.1002/pros.23741DOI Listing
March 2019
12 Reads

Mushroom poisoning: A proposed new clinical classification.

Toxicon 2019 Jan 12;157:53-65. Epub 2018 Nov 12.

Dept. for Clinical Toxicology at II, Med. Klinik, TU, München, Munich, Germany.

Mushroom poisoning is a significant and increasing form of toxin-induced-disease. Existing classifications of mushroom poisoning do not include more recently described new syndromes of mushroom poisoning and this can impede the diagnostic process. We reviewed the literature on mushroom poisoning, concentrating on the period since the current major classification published in 1994, to identify all new syndromes of poisoning and organise them into a new integrated classification, supported by a new diagnostic algorithm. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00410101183072
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http://dx.doi.org/10.1016/j.toxicon.2018.11.007DOI Listing
January 2019
102 Reads

2,4-Dimethylaniline generates phosphorylated histone H2AX in human urothelial and hepatic cells through reactive oxygen species produced by cytochrome P450 2E1.

Arch Toxicol 2018 10 21;92(10):3093-3101. Epub 2018 Aug 21.

Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, 6-21-1 Nagao, Tama-ku, Kawasaki, Kanagawa, 214-8585, Japan.

The Japanese Ministry of Health, Labour, and Welfare recently reported an outbreak of bladder cancer among workers who handled aromatic amines in Japan. 2,4-dimethylaniline (2,4-DMA) is one of the chemicals that workers are considered to have the most opportunities to be exposed. Genotoxic events are known to be crucial steps in the initiation of cancer. Read More

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http://link.springer.com/10.1007/s00204-018-2289-6
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http://dx.doi.org/10.1007/s00204-018-2289-6DOI Listing
October 2018
32 Reads

Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes.

Biomed Pharmacother 2018 Mar 20;99:561-569. Epub 2018 Feb 20.

Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous studies show that disulfiram (DSF), an anti-alcoholism drug with a low toxicity profile, demonstrates anticancer behaviors. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07533322173545
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http://dx.doi.org/10.1016/j.biopha.2018.01.109DOI Listing
March 2018
12 Reads
2.023 Impact Factor

A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing.

Acta Biomater 2018 07 25;75:63-74. Epub 2018 May 25.

Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland. Electronic address:

The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system was fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. Read More

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http://dx.doi.org/10.1016/j.actbio.2018.05.039DOI Listing
July 2018
22 Reads

A Chemosensitizer Drug: Disulfiram Prevents Doxorubicin-Induced Cardiac Dysfunction and Oxidative Stress in Rats.

Cardiovasc Toxicol 2018 10;18(5):459-470

Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur-Dist. Dhule, Maharashtra, 425405, India.

In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Read More

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http://dx.doi.org/10.1007/s12012-018-9458-yDOI Listing
October 2018
25 Reads
1 Citation
2.060 Impact Factor

Trichloroethylene exposure results in the phosphorylation of histone H2AX in a human hepatic cell line through cytochrome P450 2E1-mediated oxidative stress.

J Appl Toxicol 2018 09 3;38(9):1224-1232. Epub 2018 May 3.

Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, Japan.

Trichloroethylene (TCE), a chlorinated hydrocarbon, was recently reclassified as a human carcinogen by the International Agency for Research on Cancer. Genotoxic events are known to be crucial steps in the initiation of cancer. The genotoxic properties of TCE have been examined in many studies using a standard battery of genotoxicity tests both in vitro and in vivo. Read More

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http://dx.doi.org/10.1002/jat.3632DOI Listing
September 2018
6 Reads

Disulfiram-based disulfides as narrow-spectrum antibacterial agents.

Bioorg Med Chem Lett 2018 05 10;28(8):1298-1302. Epub 2018 Mar 10.

Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA; Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA. Electronic address:

Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. Read More

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http://dx.doi.org/10.1016/j.bmcl.2018.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893419PMC
May 2018
13 Reads

Fulminant encephalopathy with unusual brain imaging in disulfiram toxicity.

Neurology 2018 03 9;90(11):518-519. Epub 2018 Feb 9.

From Sir Jamshedjee Jeejeebhoy Hospital, Mumbai, India.

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http://dx.doi.org/10.1212/WNL.0000000000005125DOI Listing
March 2018
31 Reads
8.290 Impact Factor

Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma.

J Neurooncol 2018 May 27;138(1):105-111. Epub 2018 Jan 27.

Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, 63110, USA.

Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we have previously reported our initial dose-escalation results combining disulfiram with adjuvant temozolomide and established the maximum tolerated dose (MTD) as 500 mg per day. Here we report the final results of the phase I study including an additional dose-expansion cohort of disulfiram with concurrent copper. Read More

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http://dx.doi.org/10.1007/s11060-018-2775-yDOI Listing
May 2018
39 Reads

Repurposing disulfiram for cancer therapy via targeted nanotechnology through enhanced tumor mass penetration and disassembly.

Acta Biomater 2018 03 30;68:113-124. Epub 2017 Dec 30.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter St., Columbia, SC 29208, United States. Electronic address:

Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, degrades to therapeutically active diethyldithiocarbamate (DDTC) in the body by reduction. Hereby, we developed a redox sensitive DDTC-polymer conjugate for targeted cancer therapy. It was found that the DDTC-polymer conjugate modified with a β-d-galactose receptor targeting ligand can self-assemble into LDNP nanoparticle and efficiently enter cancer cells by receptor-mediated endocytosis. Read More

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http://dx.doi.org/10.1016/j.actbio.2017.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803356PMC
March 2018
17 Reads

The Intraocular Lens as a Drug Delivery Device: In Vitro Screening of Pharmacologic Substances for the Prophylaxis of Posterior Capsule Opacification.

Invest Ophthalmol Vis Sci 2017 12;58(14):6408-6418

Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.

Purpose: Numerous pharmacologic substances have been proposed for preventing posterior capsule opacification (PCO). The following trial was to compare those drugs to find more suitable options. IOL should then be modified by the pharmaceuticals as a drug-delivery device. Read More

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http://dx.doi.org/10.1167/iovs.17-22555DOI Listing
December 2017
23 Reads

Cell cycle specific radiosensitisation by the disulfiram and copper complex.

Oncotarget 2017 Sep 25;8(39):65900-65916. Epub 2017 Jul 25.

Radiation Oncology, Institute of Cancer Sciences, Wolfson Wohl Translational Cancer Research Center, University of Glasgow, Bearsden, Glasgow, UK.

The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Read More

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http://dx.doi.org/10.18632/oncotarget.19539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630381PMC
September 2017
9 Reads

Synergistic toxicity of epigallocatechin-3-gallate and diethyldithiocarbamate, a lethal encounter involving redox-active copper.

Free Radic Biol Med 2017 12 30;113:143-156. Epub 2017 Sep 30.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China; International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China. Electronic address:

Dithiocarbamates (DTC) are widely used in agricultural, industrial and therapeutic domains. There are ample opportunities for human exposure to DTC. Green tea extracts, with epigallocatechin-3-gallate (EGCG) being the most abundant constituent, have been used as dietary supplements for body weight reduction. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2017.09.027DOI Listing
December 2017
72 Reads

Acute pneumonitis associated with nickel carbonyl exposure in the workplace.

Clin Toxicol (Phila) 2018 03 28;56(3):223-225. Epub 2017 Jul 28.

f Pharmacotherapy , Utah Poison Control Center , Salt Lake City , UT , USA.

Background: We describe the clinical course of one industrial technician occupationally exposed to nickel carbonyl (NiC).

Case Report: A 50-year-old male industrial technician presented with complaints of nausea, myalgia, and cough to a local clinic after suspected occupational exposure to nickel carbonyl. He has no history of lung disease or smoking. Read More

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http://dx.doi.org/10.1080/15563650.2017.1355057DOI Listing
March 2018
7 Reads

BRCA1 and BRCA2 tumor suppressors protect against endogenous acetaldehyde toxicity.

EMBO Mol Med 2017 10;9(10):1398-1414

Department of Oncology, Genome Stability and Tumorigenesis Group, The CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK

Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. Read More

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http://embomolmed.embopress.org/lookup/doi/10.15252/emmm.201
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http://dx.doi.org/10.15252/emmm.201607446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623864PMC
October 2017
86 Reads

In Vitro Collapsing Colon Cancer Cells by Selectivity of Disulfiram-Loaded Charge Switchable Nanoparticles Against Cancer Stem Cells.

Recent Pat Anticancer Drug Discov 2017 ;12(3):260-271

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria. Egypt.

Background: Different strategies against colon cancer are accompanied by treatment failure, because of drug toxicity toward normal cells and cancer stem cells (CSCs) resistance. However, previous patent evaluated liposome that encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity. Read More

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http://dx.doi.org/10.2174/1574892812666170424144925DOI Listing
November 2017
16 Reads

Subacute alcohol and/or disulfiram intake affects bioelements and redox status in rat testes.

Food Chem Toxicol 2017 Jul 24;105:44-51. Epub 2017 Mar 24.

Department for Toxicology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address:

The aim of the study was to investigate if alcohol and disulfiram (DSF) individually and in combination affect bioelements' and red-ox homeostasis in testes of the exposed rats. The animals were divided into groups according to the duration of treatments (21 and/or 42 days): C/C groups (controls); OL and OL groups (0.5 mL olive oil intake); A groups (3 mL 20% ethanol intake); DSF groups (178. Read More

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http://dx.doi.org/10.1016/j.fct.2017.03.041DOI Listing
July 2017
16 Reads

1,2-Dichloropropane generates phosphorylated histone H2AX via cytochrome P450 2E1-mediated metabolism.

Toxicol Lett 2017 Apr 12;272:60-67. Epub 2017 Mar 12.

Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, Japan.

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated solvent, was recently classified as carcinogenic. Genotoxic events are known as a crucial step in the initiation of cancer. However, studies on the genotoxicity of 1,2-DCP are very limited, particularly studies investigating the mechanism behind DNA damage by 1,2-DCP. Read More

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http://dx.doi.org/10.1016/j.toxlet.2017.03.009DOI Listing
April 2017
51 Reads

Comment on: Sensory-motor axonal polyneuropathy involving cranial nerves: An uncommon manifestation of disulfiram toxicity (Santos et al., Clin Neurol Neurosurg, 152:12-15, 2016).

Clin Neurol Neurosurg 2017 03 18;154:109. Epub 2017 Jan 18.

Department of Anesthesiology and Critical Care Medicine, University Hospital of Patras, School of Medicine University of Patras Rion-Patras, Greece. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S03038467173000
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http://dx.doi.org/10.1016/j.clineuro.2017.01.008DOI Listing
March 2017
12 Reads

Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium.

J Enzyme Inhib Med Chem 2017 Dec;32(1):478-489

h Department of Physiology and Pharmacology, Sapienza University , Rome , Italy.

Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. Read More

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http://dx.doi.org/10.1080/14756366.2016.1261132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010100PMC
December 2017
45 Reads
2.383 Impact Factor

Sensory-motor axonal polyneuropathy involving cranial nerves: An uncommon manifestation of disulfiram toxicity.

Clin Neurol Neurosurg 2017 Jan 10;152:12-15. Epub 2016 Nov 10.

Neurology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Porto, Portugal.

Disulfiram (tetraethylthiuram disulfide) has been used for the treatment of alcohol dependence. An axonal sensory-motor polyneuropathy with involvement of cranial pairs due to disulfiram is exceedingly rare. The authors report a unique case of an extremely severe axonal polyneuropathy involving cranial nerves that developed within weeks after a regular dosage of 500mg/day disulfiram. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03038467163039
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http://dx.doi.org/10.1016/j.clineuro.2016.11.005DOI Listing
January 2017
67 Reads

Reprofiling using a zebrafish melanoma model reveals drugs cooperating with targeted therapeutics.

Oncotarget 2016 Jun;7(26):40348-40361

Faculty of Life Sciences, The University of Manchester, Manchester, UK.

Phenotype-guided re-profiling of approved drug molecules presents an accelerated route to developing anticancer therapeutics by bypassing the target-identification bottleneck of target-based approaches and by sampling drugs already in the clinic. Further, combinations incorporating targeted therapies can be screened for both efficacy and toxicity. Previously we have developed an oncogenic-RAS-driven zebrafish melanoma model that we now describe display melanocyte hyperplasia while still embryos. Read More

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http://dx.doi.org/10.18632/oncotarget.9613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130012PMC
June 2016
54 Reads

Disulfiram and Diphenhydramine Hydrochloride Upregulate miR-30a to Suppress IL-17-Associated Autoimmune Inflammation.

J Neurosci 2016 08;36(35):9253-66

Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai 200433, China,

Unlabelled: T-helper 17 (Th17) cells play an important role in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease that affects the CNS. In the present study, MicroRNA sequencing (miRNA-seq) was performed in mouse Th0 and Th17 cells to determine the critical miRNAs that are related to Th17 differentiation. We found that miR-30a was significantly downregulated during mouse Th17 differentiation. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.4587-15.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601909PMC
August 2016
45 Reads

The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition.

Pharmacology 2016 27;98(5-6):267-271. Epub 2016 Aug 27.

Department of Pharmacology, Medical School, University of Ioannina, Ioannina, Greece.

Background/aims: Isoniazid (ISO) has been reported to inhibit the hepatic aldehyde dehydrogenase (ALDH) and to cause a disulfiram (DIS)-like reaction, albeit there are no reports demonstrating increased blood acetaldehyde levels after co-administration of ISO with alcohol. The aim of our study was to clarify whether the alcohol intolerance produced by ISO is indeed due to a typical DIS-like reaction.

Methods: DIS and ISO were administered to Wistar rats and the hepatic ethanol (ETH) metabolizing enzyme activities along with the levels of brain monoamines were determined. Read More

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http://dx.doi.org/10.1159/000448759DOI Listing
March 2017
23 Reads

Recombinant human diamine oxidase activity is not inhibited by ethanol, acetaldehyde, disulfiram, diethyldithiocarbamate or cyanamide.

Alcohol 2016 08 29;54:51-9. Epub 2016 Jun 29.

Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.

Human diamine oxidase (hDAO, EC 1.4.3. Read More

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http://dx.doi.org/10.1016/j.alcohol.2016.06.001DOI Listing
August 2016
34 Reads

Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models.

Oncotarget 2016 Dec;7(50):82200-82212

Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Disulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Read More

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http://dx.doi.org/10.18632/oncotarget.9413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347685PMC
December 2016
41 Reads

Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations.

J Nanobiotechnology 2016 Apr 21;14:32. Epub 2016 Apr 21.

Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran.

Background: A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. Read More

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http://dx.doi.org/10.1186/s12951-016-0183-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839071PMC
April 2016
58 Reads