5,595 results match your criteria Chemical Research in Toxicology [Journal]


Design, synthesis and biological activity of hydrogen peroxide responsive arylboronate melatonin hybrids.

Chem Res Toxicol 2018 Dec 18. Epub 2018 Dec 18.

Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) have been associated with the development and progression of cancer and several other disease states, motivating the development of drug conjugates that can undergo a chemoselective ROS-triggered release. Melatonin (MLT) and the reactive electrophile p-benzoquinone methide (p-QM) have evidenced either cytoprotective and cytotoxic effects in biological systems, depending on the dose, cellular targets, and time of exposure. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00216DOI Listing
December 2018

Kinetics of Glutathione Depletion and Antioxidant Gene Expression as Indicators of Chemical Modes of Action Assessed in vitro in Mouse Hepatocytes with Enhanced Glutathione Synthesis.

Chem Res Toxicol 2018 Dec 14. Epub 2018 Dec 14.

Here we report a vertically integrated in vitro - in silico study that aims to elucidate the molecular initiating events involved in the induction of oxidative stress (OS) by seven diverse chemicals (cumene hydroperoxide, t-butyl hydroperoxide, hydroquinone, t-butyl hydroquinone, bisphenol A, Dinoseb, and perflourooctanoic acid). To that end, we probe the relationship between chemical properties, cell viability, glutathione (GSH) depletion and antioxidant gene expression. Concentration-dependent effects on cell viability were assessed by MTT assay in two Hepa-1 derived mouse liver cell lines: a control plasmid vector transfected cell line (Hepa-V), and a cell line with increased glutamate-cysteine ligase (GCL) activity and GSH content (CR17). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00259DOI Listing
December 2018

Development of new epoxy resin monomers - A delicate balance between skin allergy and polymerization properties.

Chem Res Toxicol 2018 Dec 13. Epub 2018 Dec 13.

Epoxy resin monomers (ERMs) are used as building blocks for thermosetting polymers in applications where strong, flexible, and light-weight materials are required. Most epoxy resins are polymers of diglycidyl ether of bisphenol A (DGEBA). It is highly allergenic and causes occupational allergic contact dermatitis and contact allergy in the general population. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00169DOI Listing
December 2018

Reducing Holomycin Thiosulfonate to its Disulfide with Thiols.

Chem Res Toxicol 2018 Dec 7. Epub 2018 Dec 7.

The dithiolopyrrolone (DTP) natural products contain a unique ene-disulfide that is essential for their antimicrobial and anticancer activities. The ene-disulfide in some DTPs is oxidized to a cyclic thiosulfonate, but it is unknown how the DTP thiosulfonates react with biomolecules. We studied the reactivity of the thiosulfonate derivative of the DTP holomycin, oxo-holomycin, and discovered a unique redox reaction: oxo-holomycin is reduced to its parent disulfide, while oxidizing small molecule and protein thiols to disulfides. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00243DOI Listing
December 2018

Emissions of free radicals, carbonyls, and nicotine from the NIDA Standardized Research Electronic Cigarette and comparison to similar commercial devices.

Chem Res Toxicol 2018 Dec 7. Epub 2018 Dec 7.

E-cigarettes (e-cigs) are a diverse and continuously evolving group of products with four generations currently in the market. The National Institute on Drug Abuse (NIDA) standardized research e-cigarette (SREC) is intended to provide researchers with a consistent e-cig device with known characteristics. Thus, we conducted laboratory-based characterizations of oxidants and nicotine in aerosols produced from SREC and other closed-system, breath-activated, commercially available e-cigs (Blu and Vuse). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00235DOI Listing
December 2018

Pharmacokinetics of three neonicotinoid insecticides upon contact exposure in the western honey bee, Apis mellifera.

Chem Res Toxicol 2018 Dec 10. Epub 2018 Dec 10.

Neonicotinoid insecticides differ in their acute contact toxicity to honey bees. Here we investigated the uptake, metabolic fate and excretion of imidacloprid and two much less toxic chemotypes, thiacloprid and acetamiprid, upon contact expo-sure in honey bees as ADME data for this mode of entry are lacking. Pharmacokinetic parameters were analyzed by track-ing a 14C-label and HPLC coupled to ESI-MS. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00315DOI Listing
December 2018

Estrogen Metabolism in African-American Women with and without Breast Cancer: A Pilot Study.

Chem Res Toxicol 2018 Dec 11. Epub 2018 Dec 11.

Studies in Caucasian women have shown that the formation of estrogen-DNA adducts is greater in women at high risk for breast cancer or already diagnosed with the disease. To begin investigating whether the role of estrogens in the etiology of breast cancer is similar in African-American (AA) women, a saliva sample and a spot urine sample were collected from 19 AA women with breast cancer and 23 AA women not diagnosed with breast cancer. In the urine samples, twenty estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and the then ratio of adducts to metabolites and estrogen conjugates was calculated for each sample. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00285DOI Listing
December 2018

Evaluation of In Vitro Mitochondrial Toxicity Assays and Physicochemical Properties for Prediction of Organ Toxicity Using 228 Pharmaceutical Drugs.

Chem Res Toxicol 2018 Dec 10. Epub 2018 Dec 10.

Mitochondrial toxicity has been shown to contribute to a variety of organ toxicities such as liver, cardiac and kidney. In the past decades, two high throughput applicable screening assays (isolated rat liver mitochondria; glucose-galactose grown HepG2 cells) to assess mitochondrial toxicity have been deployed in many pharmaceutical companies and numerous publications have demonstrated its usefulness for mechanistic investigations. However, only two publications have demonstrated the utility of these screens as a predictor of human drug induced liver injury. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00246DOI Listing
December 2018

Aflatoxin-guanine DNA Adducts and Oxidatively-induced DNA Damage in Aflatoxin-treated Mice in vivo as Measured by Liquid Chromatography-Tandem Mass Spectrometry with Isotope-dilution.

Chem Res Toxicol 2018 Dec 11. Epub 2018 Dec 11.

Dietary exposure to aflatoxin B1 (AFB1) is a significant contributor to the incidence of hepatocellular carcinomas globally. AFB1-exposure leads to the formation of AFB1-N7-guanine (AFB1-N7-Gua) and two diastereomers of the imidazole ring-opened 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B1 (AFB1-FapyGua) in DNA. These adducts lead to G → T transversion mutations with the ring-opened adduct being more mutagenic than the cationic species. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00202DOI Listing
December 2018

Chromatin Modifications in Toxicology.

Authors:
James J Galligan

Chem Res Toxicol 2018 Dec 6. Epub 2018 Dec 6.

Department of Pharmacology and Toxicology, College of Pharmacy , University of Arizona , Tucson , Arizona 85721 , United States.

Histone modifications regulate chromatin structure and function. Primary and secondary metabolites stemming from environmental and chemical exposures may play a critical role in the underlying epigenomic state of a cell through covalent histone modifications. Future investigations should be focused on characterizing the "Histone Code" when performing toxicogenomic analyses. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00267DOI Listing
December 2018
2 Reads

Key Characteristics Approach to Carcinogenic Hazard Identification.

Chem Res Toxicol 2018 Dec 6. Epub 2018 Dec 6.

Division of Environmental Health Sciences, School of Public Health , University of California , Berkeley , California 94720 , United States.

Evaluating carcinogenic mechanisms is a challenging part of hazard identification, as mechanistic data are both voluminous and diverse. An evaluation approach based on 10 key characteristics of human carcinogens provides a holistic and unbiased way to tackle this challenge. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00321
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http://dx.doi.org/10.1021/acs.chemrestox.8b00321DOI Listing
December 2018
7 Reads

In vitro DNA Adduction Resulting from Metabolic Activation of Diosbulbin B and 8-Epidiosbulbin E Acetate.

Chem Res Toxicol 2018 Dec 6. Epub 2018 Dec 6.

Diosbulbin B (DBB) and 8-epidiosbulbin E acetate (EEA), belonging to furan-containing diterpenoid lactones, are the primary components of Dioscorea bulbifera L. (DB), a traditional Chinese medicine herb. Our earlier studies indicated that consumption of DBB or EEA induced acute hepatotoxicities. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00071DOI Listing
December 2018
2 Reads

Correlation between Glyoxal-Induced DNA Cross-Links and Hemoglobin Modifications in Human Blood Measured by Mass Spectrometry.

Chem Res Toxicol 2018 Dec 18. Epub 2018 Dec 18.

Department of Chemistry and Biochemistry , National Chung Cheng University , 168 University Road , Ming-Hsiung, Chia-Yi 62142 , Taiwan.

Glyoxal is an oxoaldehyde generated from the degradation of glucose-protein conjugates and from lipid peroxidation in foods and in vivo, and it is also present in the environment (e.g., cigarette smoke). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00264DOI Listing
December 2018

Plasma and Hepatic Concentrations of Chemicals after Virtual Oral Administrations Extrapolated Using Rat Plasma Data and Simple Physiologically Based Pharmacokinetic Models.

Chem Res Toxicol 2018 Dec 18. Epub 2018 Dec 18.

Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , 3-3165 Higashi-tamagawa Gakuen , Machida, Tokyo 194-8543 , Japan.

Only a small fraction of chemicals possesses adequate in vivo toxicokinetic data for assessing potential hazards. The aim of the present study was to model the plasma and hepatic pharmacokinetics of more than 50 disparate types of chemicals and drugs after virtual oral administrations in rats. The models were based on reported pharmacokinetics determined after oral administration to rats. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00307
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http://dx.doi.org/10.1021/acs.chemrestox.8b00307DOI Listing
December 2018
2 Reads

Chemicals and Drugs Forming Reactive Quinone and Quinone Imine Metabolites.

Chem Res Toxicol 2018 Nov 30. Epub 2018 Nov 30.

Quinones and quinone imines are highly reactive metabolites (RMs) able to induce dangerous effects in vivo. They are responsible for all kinds of toxicity: e.g. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00213DOI Listing
November 2018

Disruption of Kidney Metabolism in Rats after Subchronic Combined Exposure to Low-Dose Cadmium and Chlorpyrifos.

Chem Res Toxicol 2018 Nov 30. Epub 2018 Nov 30.

Cadmium (Cd) and chlorpyrifos (CPF) often coexist in the environment and induce combined toxicity to organisms. Here we studied the combined nephrotoxicity of environmentally relevant low doses of Cd and CPF. We treated the mice for 90 days with different doses of Cd and CPF and their mixtures via oral gavage. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00219DOI Listing
November 2018
4 Reads

Engineering Protective Polymer Coatings for Liver Microtissues.

Chem Res Toxicol 2018 Nov 30. Epub 2018 Nov 30.

Three-dimensional (3D) hepatocyte microtissues (MT), also known as spheroids, have proven to be advantageous in providing more accurate information and physiologically relevant and predictive data for liver-related in vivo tests; therefore, spheroids have increasingly been used to study hepatotoxicity, drug delivery to the liver, and tissue engineering. However, variabilities in the generation of 3D MT remain a major challenge. Methods which encapsulate and protect hepatocytes offer a promising pathway in prolonging cell survival, as well as maintaining its pristine cell functions. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00120DOI Listing
November 2018

Perfluorododecanoic acid blocks rat Leydig cell development during prepuberty.

Chem Res Toxicol 2018 Nov 29. Epub 2018 Nov 29.

Perfluorododecanoic acid (PFDoA) has been used as a surfactant and may have reproductive toxicity. However, whether PFDoA influences Leydig cell development during prepuberty remains unknown. In the present study, 21-day-old male Sprague Dawley rats were gavaged 0, 5 or 10 mg/kg PFDoA from postnatal day 21 to 35. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00241DOI Listing
November 2018
5 Reads
3.529 Impact Factor

Structural and Metal Ion Effects on Human Topoisomerase IIα Inhibition by α-(N)-Heterocyclic Thiosemicarbazones.

Chem Res Toxicol 2018 Nov 28. Epub 2018 Nov 28.

Our previous research has shown that α-(N)-heterocyclic thiosemicarbazone (TSC) metal complexes inhibit human topoisomerase IIα (TopoIIα), while the ligands without metals do not. To find out the structural elements of TSC that are important for inhibiting TopoIIα, we have synthesized two series of α-(N)-heterocyclic TSCs with various substrate ring segments, side chain substitutions and metal ions, and we have examined their activities in TopoIIα-mediated plasmid DNA relaxation and cleavage assays. Our goal is to explore the structure-activity relationship of α-(N)-heterocyclic TSCs and their effect on TopoIIα. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00204DOI Listing
November 2018

Toxicant deposition and transport in alveolus: a classical density functional prediction.

Chem Res Toxicol 2018 Nov 27. Epub 2018 Nov 27.

The deposition and transport of toxicants on pulmonary surfactant is an important process in human health and medical care. We have introduced classical density functional theory (CDFT) to provide insight into this process. Nine typical toxicants in PM2. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00272DOI Listing
November 2018

Dermal absorption of pesticide residues.

Chem Res Toxicol 2018 Nov 23. Epub 2018 Nov 23.

Current guidance for dermal exposure assessment of plant protection products typically uses in vitro skin penetration data for the active ingredient when applied as both the concentrated product and relevant spray dilutions thereof. However, typical re-entry scenarios involve potential skin exposure to a 'dried residue' of the spray dilution, from which the absorption of a pesticide may be quite different. The research reported in this paper has shown: [1] The method to assess the transfer of dried pesticide residues from a surface to the skin is reproducible for four active ingredients of diverse physicochemical properties, after their application in commercially relevant formulations. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00227DOI Listing
November 2018
1 Read

Structural insights of stereospecific inhibition of human acetylcholinesterase by VX and subsequent reactivation by HI-6.

Chem Res Toxicol 2018 Nov 21. Epub 2018 Nov 21.

Over 50 years ago, the toxicity of irreversible organophosphate inhibitors targeting human acetylcholinesterase (hAChE) were observed to be stereospecific. The therapeutic reversal of hAChE inhibition by reactivators has also been shown to depend on the stereochemistry of the inhibitor. To gain clarity on the mechanism of stereospecific inhibition, the X-ray crystallographic structures hAChE inhibited by a racemic mixture of VX (P) and its enantiomers were obtained. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00294DOI Listing
November 2018
2 Reads

Fluorescence-based high throughput screening technologies for natural chloride ion channel blockers.

Chem Res Toxicol 2018 Nov 20. Epub 2018 Nov 20.

Chloride channels represent a group of potential drug targets, their blockers showed significant protecting effect on impaired cells by modulating apoptosis, autophagy and other cell signals. However, clinical drugs with chloride channel inhibitory properties have not yet been developed. Natural product extract becomes an underlying candidate satisfied the clinical requirements for its low toxicity, low cost and abundant sources. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00205
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http://dx.doi.org/10.1021/acs.chemrestox.8b00205DOI Listing
November 2018
4 Reads

Nanosafety Research-An Ongoing Story.

Chem Res Toxicol 2018 Nov;31(11):1105

Nano Cell Interactions , INM - Leibniz Institute for New Materials , 66123 Saarbruecken , Germany.

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http://dx.doi.org/10.1021/acs.chemrestox.8b00325DOI Listing
November 2018

A Difference in Internal Exposure Makes Newly Weaned Mice More Susceptible to the Hepatotoxicity of Retrorsine Than Adult Mice.

Chem Res Toxicol 2018 Nov 29. Epub 2018 Nov 29.

Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , Liaoning 110016 , P. R. China.

Pyrrolizidine alkaloids (PAs) are known hepatotoxins. Children have been reported to be particularly susceptible to PA-induced hepatotoxicity. To improve our understanding of the mechanisms of the age-dependent difference in susceptibility to PA hepatotoxicity, a comparative study of hepatotoxicities of retrorsine (RTS), a representative PA, was performed in newly weaned (3-4 weeks of age) and adult mice (8-12 weeks of age). Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00220
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http://dx.doi.org/10.1021/acs.chemrestox.8b00220DOI Listing
November 2018
6 Reads

Effects of Charcoal on Carbonyl Delivery from Commercial, Research, and Make-Your-Own Cigarettes.

Chem Res Toxicol 2018 Nov 28. Epub 2018 Nov 28.

Department of Public Health Sciences , Pennsylvania State University Tobacco Center of Regulatory Science (TCORS), Pennsylvania State University College of Medicine , Hershey , Pennsylvania 17033 , United States.

Previous literature has shown that adding charcoal to cigarette filters can have varying effects on the delivery of toxic carbonyls depending on filter design, amount of charcoal, and puffing profiles. However, these studies have relied on either comparisons between commercially available charcoal and noncharcoal filtered cigarettes or experimental modification of filters to insert a charcoal plug into existing cellulose acetate filters. Make-your-own (MYO) cigarettes can help obviate many of the potential pitfalls of previous studies; thus, we conducted studies using commercial charcoal cigarettes and MYO cigarettes to determine the effects of charcoal on carbonyl delivery. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00211
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http://dx.doi.org/10.1021/acs.chemrestox.8b00211DOI Listing
November 2018
4 Reads

Delayed Puberty by Ziram Is Associated with Down Regulation of Testicular Phosphorylated AKT1 and SIRT1/PGC-1α Signaling.

Chem Res Toxicol 2018 Nov 27. Epub 2018 Nov 27.

Department of Obstetrics and Gynecology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , 109 Xueyuan West Road , Wenzhou , Zhejiang 325027 , China.

Ziram is a dimethyldithiocarbamate fungicide, which may influence the male reproductive system as a potential endocrine disruptor. We interrogated the disruption of ziram on rat progenitor Leydig cell development. Prepubertal male Sprague-Dawley rats were orally treated with 0, 2, 4, or 8 mg/kg ziram for 2 weeks. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00201
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http://dx.doi.org/10.1021/acs.chemrestox.8b00201DOI Listing
November 2018
5 Reads
3.530 Impact Factor

IL-27 Production and Regulation in Human Dendritic Cells Treated with the Chemical Sensitizer NiSO.

Chem Res Toxicol 2018 Nov 27. Epub 2018 Nov 27.

Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de Pharmacie , Université Paris-Saclay , 92290 Châtenay-Malabry , France.

Allergic contact dermatitis (ACD) is a major cause of occupational skin disease, and nickel is among the most prevalent contact allergens. Dendritic cells (DC) play an important role in ACD and in the type of the ensuing immune response through differential phenotypes and cytokine production. The interleukin (IL)-12 cytokine family is composed of heterodimeric cytokines sharing homology at the subunit, receptors and signaling levels. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00203
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http://dx.doi.org/10.1021/acs.chemrestox.8b00203DOI Listing
November 2018
9 Reads

Oxidation of 8-Oxo-7,8-dihydro-2'-deoxyguanosine Leads to Substantial DNA-Histone Cross-Links within Nucleosome Core Particles.

Chem Res Toxicol 2018 Nov 19. Epub 2018 Nov 19.

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry , Nankai University , Tianjin 300071 , China.

8-Oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodGuo) is a common primary product of cellular oxidative DNA damage. 8-OxodGuo is more readily oxidized than 2'-deoxyguanosine (dG); a two-electron oxidation generates a highly reactive intermediate (OG), which forms covalent adducts with nucleophiles, including OH, free amines, and the side chains of amino acids such as lysine. We determined here that KFe(CN) oxidation of 8-oxodGuo in nucleosome core particles (NCPs) produces high yields, quantitative (i. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00244DOI Listing
November 2018
5 Reads

Cytochrome P450 1A1, 2C9, 2C19, and 3A4 Polymorphisms Account for Interindividual Variability of Toxicological Drug Metabolism in Cynomolgus Macaques.

Chem Res Toxicol 2018 Nov 19. Epub 2018 Nov 19.

Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo 194-8543 , Japan.

Cytochromes P450 (P450s) and their genetic variants in humans are important drug-metabolizing enzymes partly accounting for interindividual variations in drug metabolism and toxicity. However, these genetic variants in P450s have not been fully investigated in cynomolgus macaques, a nonhuman primate species widely used in toxicological studies. In this study, genetic variants found in cynomolgus CYP1A1, CYP2C9 (formerly CYP2C43), CYP2C19 (CYP2C75), and CYP3A4 (CYP3A8) were assessed on functional importance. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00257
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http://dx.doi.org/10.1021/acs.chemrestox.8b00257DOI Listing
November 2018
2 Reads

Role of Human Aldo-Keto Reductases in the Metabolic Activation of the Carcinogenic Air Pollutant 3-Nitrobenzanthrone.

Chem Res Toxicol 2018 Nov 8;31(11):1277-1288. Epub 2018 Nov 8.

Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation , Grosshansdorf 22927 , Germany.

3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen detected in diesel exhaust particulate and ambient air pollution. It requires metabolic activation via nitroreduction to promote DNA adduct formation and tumorigenesis. NAD(P)H:quinone oxidoreductase 1 (NQO1) has been previously implicated as the major nitroreductase responsible for 3-NBA activation, but it has recently been reported that human aldo-keto reductase 1C3 (AKR1C3) displays nitroreductase activity toward the chemotherapeutic agent PR-104A. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00250DOI Listing
November 2018

The carbamate aldicarb altered the gut microbiome, metabolome and lipidome of C57BL/6J mice.

Chem Res Toxicol 2018 Nov 8. Epub 2018 Nov 8.

The gut microbiome is highly involved in numerous aspects of host physiology, from energy harvest to stress response, and can confer many benefits to the host. The gut microbiome development could be affected by genetic and environmental factors, including the pesticides. The carbamate insecticide aldicarb has been extensively used in agriculture, which raises serious public health concern. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00179
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http://dx.doi.org/10.1021/acs.chemrestox.8b00179DOI Listing
November 2018
3 Reads

2,6-Dihydroxybenzaldehyde Analogues of the Iron Chelator Salicylaldehyde Isonicotinoyl Hydrazone: Increased Hydrolytic Stability and Cytoprotective Activity against Oxidative Stress.

Chem Res Toxicol 2018 Nov 5;31(11):1151-1163. Epub 2018 Nov 5.

Faculty of Pharmacy in Hradec Králové , Charles University , Akademika Heyrovského 1203 , 500 05 Hradec Králové , Czech Republic.

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a small molecule and lipophilic chelating agent that firmly binds ferric ions from the cellular labile iron pool and is able to protect various tissues against oxidative damage. Previously, SIH possessed the best ratio of cytoprotective efficiency to toxicity among various iron chelators, including the desferrioxamine, deferiprone, and deferasirox used in clinical practice. Here, we prepared a series of 2,6-dihydroxybenzaldehyde aroylhydrazones as SIH analogues with an additional hydroxyl group that can be involved in the chelation of metal ions. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00165DOI Listing
November 2018
5 Reads

Targeted and Untargeted Detection of DNA Adducts of Aromatic Amine Carcinogens in Human Bladder by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

Chem Res Toxicol 2018 Nov 19. Epub 2018 Nov 19.

Department of Pharmacological Sciences , Stony Brook University , Stony Brook , New York 11794 , United States.

Epidemiological studies have linked aromatic amines (AAs) from tobacco smoke and some occupational exposures with bladder cancer risk. Several epidemiological studies have also reported a plausible role for structurally related heterocyclic aromatic amines present in tobacco smoke or formed in cooked meats with bladder cancer risk. DNA adduct formation is an initial biochemical event in bladder carcinogenesis. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00268
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http://dx.doi.org/10.1021/acs.chemrestox.8b00268DOI Listing
November 2018
5 Reads

Correlation of Platinum Cytotoxicity to Drug-DNA Adduct Levels in a Breast Cancer Cell Line Panel.

Chem Res Toxicol 2018 Nov 19. Epub 2018 Nov 19.

Department of Internal Medicine, Division of Hematology and Oncology , University of California Davis , Sacramento , California 95817 , United States.

Platinum drugs, including carboplatin and oxaliplatin, are commonly used chemotherapy drugs that kill cancer cells by forming toxic drug-DNA adducts. These drugs have a proven, but modest, efficacy against several aggressive subtypes of breast cancer but also cause several side effects that can lead to the cessation of treatment. There is a clinical need to identify patients who will respond to platinum drugs in order to better inform clinical decision making. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00170DOI Listing
November 2018
1 Read

Lateral Flow Assessment and Unanticipated Toxicity of Kratom.

Chem Res Toxicol 2018 Nov 16. Epub 2018 Nov 16.

ABiox Company, 720 East First Street , Newberg , Oregon 97132 , United States.

The leaves of the Mitragynine speciosia tree (also known as Kratom) have long been chewed, smoked, or brewed into a tea by people in Southeastern Asian countries, such as Malaysia and Thailand. Just this past year, the plant Kratom gained popularity in the United States as a "legal opioid" and scheduling it as a drug of abuse is currently pending. The primary alkaloid found in Kratom is a μ-opioid receptor agonist, mitragynine, whose structure contains a promising scaffold for immunopharmacological use. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00218
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http://dx.doi.org/10.1021/acs.chemrestox.8b00218DOI Listing
November 2018
21 Reads

Atypical Gasdermin D and Mixed Lineage Kinase Domain-like Protein Leakage Aggravates Tetrachlorobenzoquinone-Induced Nod-like Receptor Protein 3 Inflammasome Activation.

Chem Res Toxicol 2018 Nov 9. Epub 2018 Nov 9.

Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing 400715 , People's Republic of China.

Our previous study showed that tetrachlorobenzoquinone (TCBQ) mediated the activation of Nod-like receptor protein 3 (NLRP3) inflammasome, which involves K efflux, reactive oxygen species (ROS) production, and mitochondrial DNA damage. In addition, TCBQ down-regulates NLRP3 ubiquitination and promotes the activation of NLRP3 inflammasome. However, the induction of NLRP3 inflammasome by atypical pathways has not yet been characterized. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00306DOI Listing
November 2018

Discovery of Novel N-(4-Hydroxybenzyl)valine Hemoglobin Adducts in Human Blood.

Chem Res Toxicol 2018 Nov 19. Epub 2018 Nov 19.

Department of Environmental Science and Analytical Chemistry , Stockholm University , SE-106 91 Stockholm , Sweden.

Humans are exposed to a wide range of electrophilic compounds present in our diet and environment or formed endogenously as part of normal physiological processes. These electrophiles can modify nucleophilic sites of proteins and DNA to form covalent adducts. Recently, powerful untargeted adductomic approaches have been developed for systematic screening of these adducts in human blood. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00173DOI Listing
November 2018

Prediction of Farnesoid X Receptor Disruptors with Machine Learning Methods.

Chem Res Toxicol 2018 Nov 8;31(11):1128-1137. Epub 2018 Nov 8.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , China.

The farnesoid X receptor (FXR) emerges as a promising drug target involved in regulating various metabolic pathways, yet some xenobiotic compounds binding to FXR would be an important determinant to induce the receptor dysfunctions that lead to undesirable side effects. Thus, it is critical to identify potential xenobiotics that disrupt normal FXR functions. In this work, five machine learning methods coupled with eight molecular fingerprints and 20 molecular descriptors were used to develop classification models for prediction of FXR binders. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00162
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http://dx.doi.org/10.1021/acs.chemrestox.8b00162DOI Listing
November 2018
3 Reads
3.529 Impact Factor

Age-Associated Methylation in Human Hemoglobin and Its Stability on Dried Blood Spots As Analyzed by Nanoflow Liquid Chromatography Tandem Mass Spectrometry.

Chem Res Toxicol 2018 Nov 2;31(11):1240-1247. Epub 2018 Nov 2.

Department of Chemistry and Biochemistry , National Chung Cheng University , 168 University Road, Ming-Hsiung, Chia-Yi 62142 , Taiwan.

Methylation of biomolecules is involved in many important biological processes. The contributing methylating agents arise from endogenous and exogenous sources (such as cigarette smoking). Human hemoglobin is easily accessible from blood and has been used as a molecular dosimeter for monitoring chemical exposure. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00224DOI Listing
November 2018

Toxicological Antagonism among Welding Fume Metals: Inactivation of Soluble Cr(VI) by Iron.

Chem Res Toxicol 2018 Nov 6;31(11):1172-1184. Epub 2018 Nov 6.

Department of Pathology and Laboratory Medicine , Brown University , 70 Ship Street , Providence , Rhode Island 02912 , United States.

Epidemiological studies in chromate production have established hexavalent chromium as a potent lung carcinogen. Inhalation of chromium(VI) most often occurs in mixtures with other metals as among stainless steel welders, which is the largest occupational group with Cr(VI) exposure. Surprisingly, carcinogenicity of Cr(VI)-containing welding fumes is moderate and not consistently higher than that of Cr-free welding. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00182
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http://dx.doi.org/10.1021/acs.chemrestox.8b00182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247247PMC
November 2018
5 Reads

Tetrachlorobenzoquinone-Induced Nrf2 Confers Neuron-like PC12 Cells Resistance to Endoplasmic Reticulum Stress via Regulating Glutathione Synthesis and Protein Thiol Homeostasis.

Chem Res Toxicol 2018 Nov 2;31(11):1230-1239. Epub 2018 Nov 2.

Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715.

Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ) is toxic to neuron-like cells, which is related to endoplasmic reticulum (ER) stress-induced apoptosis. However, it remains unclear whether TCBQ causes the opening of cellular defense responses. Here we found that activation of nuclear factor erythroid-derived 2-like 2 (Nrf2) triggered an adaptive response against the neurotoxicity induced by TCBQ through the upregulation of intracellular glutathione (GSH) levels in rat pheochromocytoma PC12 cells. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00209
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http://dx.doi.org/10.1021/acs.chemrestox.8b00209DOI Listing
November 2018
5 Reads

Molecular and Functional Characterization of N-Acetyltransferases NAT1 and NAT2 in Cynomolgus Macaque.

Chem Res Toxicol 2018 Nov 25;31(11):1269-1276. Epub 2018 Oct 25.

Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo 194-0042 , Japan.

Arylamine N-acetyltransferases (NATs) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics, and their molecular characteristics have been extensively investigated in humans, but not in cynomolgus macaques, nonhuman primate species important for drug metabolism studies. In this study, cynomolgus NAT1 and NAT2 cDNAs were isolated from livers. NAT1 and NAT2 were characterized by molecular analyses and drug-metabolizing assays. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00236DOI Listing
November 2018

Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity.

Chem Res Toxicol 2018 Nov 17;31(11):1119-1127. Epub 2018 Oct 17.

Centre for Molecular Informatics, Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , United Kingdom.

Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs' biological targets. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00159
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http://dx.doi.org/10.1021/acs.chemrestox.8b00159DOI Listing
November 2018
6 Reads

Interdisciplinary Approaches and Expanding Scope in Chemical Toxicology.

Authors:
Yinsheng Wang

Chem Res Toxicol 2018 Oct;31(10):991

Department of Chemistry , University of California Riverside , Riverside , California 92521 , United States.

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http://dx.doi.org/10.1021/acs.chemrestox.8b00261DOI Listing
October 2018

Mechanisms of Fumonisin B1 Toxicity: A Computational Perspective beyond the Ceramide Synthases Inhibition.

Chem Res Toxicol 2018 Nov 2;31(11):1203-1212. Epub 2018 Nov 2.

Department of Food and Drug , University of Parma , 43124 Parma , Italy.

Fumonisins are mycotoxins produced by Fusarium fujikuroi species complex that may contaminate food and feed threatening human and animal health. Among the fumonisins group, fumonisin B1 is the most widespread and best characterized in terms of toxicity, while additional toxicological data on its congeners, such as N-acylated and hydrolyzed forms, need to be collected to support the group-based risk assessment. The inhibition of ceramide synthase has been identified as the key molecular mechanism of fumonisins toxicity resulting in modifications of sphingolipids rheostat. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00188
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http://dx.doi.org/10.1021/acs.chemrestox.8b00188DOI Listing
November 2018
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Etiology of Balkan Endemic Nephropathy: An Update on Aristolochic Acids Exposure Mechanisms.

Chem Res Toxicol 2018 Nov 22;31(11):1109-1110. Epub 2018 Oct 22.

Serbian Medical Society, Branch Niš , 18000 Niš , Serbia.

Aristolochic acid released from decaying Aristolochia clematitis weed is contaminating soil and food crops in Eastern Europe and is one of the major causes to Balkan endemic nephropathy. Measures should be taken to prevent people from being exposed to these highly potent phytotoxins. Research needs to develop remediation methods. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00291DOI Listing
November 2018

Characterizing Serpinb2 as a Modulator of TCDD-Induced Suppression of the B Cell.

Chem Res Toxicol 2018 Nov 30;31(11):1248-1259. Epub 2018 Oct 30.

Department of Biochemistry and Molecular Biology , Michigan State University , East Lansing , Michigan 48824 , United States.

2,3,7,8-Tetrachlordibenzo- p-dioxin (TCDD) is an environmental pollutant that can cause various toxic effects, including chloracne, metabolic syndrome, and immune suppression. Most of the toxicity associated with TCDD is mediated through activation of the aryl hydrocarbon receptor (AHR). Recent research has suggested the presence of a wide-range of interindividual variability in TCDD-mediated suppression of the Immunoglobulin-M (IgM) response across the human population. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00225
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http://dx.doi.org/10.1021/acs.chemrestox.8b00225DOI Listing
November 2018
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Polybrominated Diphenyl Ethers Quinone Induced Parthanatos-like Cell Death through a Reactive Oxygen Species-Associated Poly(ADP-ribose) Polymerase 1 Signaling.

Chem Res Toxicol 2018 Nov 18;31(11):1164-1171. Epub 2018 Oct 18.

Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715.

Polybrominated diphenyl ethers (PBDEs) are emerging organic environmental pollutants, which were accused of various toxic effects. Here, we studied the role of a potential PBDEs quinone metabolite, PBDEQ, on cytotoxicity, oxidative DNA damage, and the alterations of signal cascade in HeLa cells. PBDEQ exposure leads to reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) loss, lactate dehydrogenase (LDH) release, increasing terminal transferase-mediated dUTP-biotin nick end labeling (TUNEL) positive foci, and the elevation of apoptosis rate. Read More

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http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00168
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http://dx.doi.org/10.1021/acs.chemrestox.8b00168DOI Listing
November 2018
3 Reads