Current Research in Toxicology最新文献

{"title":"Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity","authors":"Aditi Dave ,&nbsp;Lucy Joshee ,&nbsp;Delon W. Barfuss ,&nbsp;Ryan Brownlee ,&nbsp;Roha Surani ,&nbsp;Sahar Anis Ali ,&nbsp;Earl G. Ford IV ,&nbsp;Elizabeth G. Pittman ,&nbsp;Anasalea V.G. Caroland ,&nbsp;Jennifer Barkin ,&nbsp;Christy C. Bridges","doi":"10.1016/j.crtox.2023.100132","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100132","url":null,"abstract":"<div><p>Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-binding protein that has been shown to bind to heavy metals and reduce their toxic effects in target cells and organs. Little is known about the effect of MT on the handing and disposition of Hg. Therefore, the current study was designed to test the hypothesis that overexpression of MT alters the corporal disposition of Hg and reduces its nephrotoxicity. Furthermore, the current study examined the transport of Hg-MT complexes in isolated proximal tubules. Rats were treated with saline or Zn followed by injection with a non-nephrotoxic (0.5 µmol kg⁻¹), moderately nephrotoxic (1.5 µmol kg⁻¹), or significantly nephrotoxic (2.25 µmol kg⁻¹) dose of HgCl₂ (containing radioactive Hg). Pretreatment with Zn increased mRNA expression of MT and enhanced accumulation of Hg in the renal cortex of male and female rats. In addition, injection with Zn also protected animals from Hg-induced nephrotoxicity. Studies using isolated proximal tubules from rabbit kidney demonstrated that Hg-MT is taken up rapidly at the apical and basolateral membranes. The current findings suggest that at least part of this uptake occurs through an endocytic process. This study is the first to examine the uptake of Hg-MT complexes in isolated proximal tubules. Overall, the findings of this study suggest that supplementation with Zn may be a viable strategy for reducing the risk of Hg intoxication in at-risk populations.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100132"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49771425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatographic analysis of selected phytosterols from Cyathea and their characterization by in silico docking to potential therapeutic targets","authors":"N. Janakiraman ,&nbsp;J. Anne Wincy ,&nbsp;M. Johnson ,&nbsp;Ana Beatriz Herminia Ducati ,&nbsp;Carlos Eduardo de Oliveira Soares ,&nbsp;Claudia Saraiva de Alencar Beltrão ,&nbsp;H.D.M. Coutinho","doi":"10.1016/j.crtox.2023.100115","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100115","url":null,"abstract":"<div><p>Separation and quantification of lupeol, stigmasterol and swertiamarin in ethanolic extracts of selected <em>Cyathea</em> species have been developed using HPTLC and an attempt is made to explore the biopotential of phytochemicals against various proteins by computational analysis. Compounds were separated using the specific mobile phase and the developed plates were sprayed with respective spraying reagents. The 3D structure of the receptor proteins viz., 1VSN, 5BNQ, 6HN8, 7DN4 and 3TJU, and the 3D SDF structures of ligands like lupeol, stigmasterol and swertiamarin were retrieved from the Protein Data Bank (PDB) and NCBI-Pub Chem Compound database respectively. The Argus 4.0.1 is computer generated drug design screening software is employed to analyze the binding affinity of test compounds against the selected proteins in the form of E-values versus potential drug targets. The docking result was saved and visualized using Discovery Studio Visualizer. The terpenoid band with R_f value 0.79 depicted the presence of lupeol in <em>C. gigantea</em> (0.04%) and <em>C. crinita</em> (0.02%)<em>.</em> The steroid band with R_f value 0.41 confirmed the presence of stigmasterol with varied frequency viz., <em>C. nilgirensis</em> (0.33%), <em>C. gigantea</em> (0.29%) and <em>C. crinita</em> (0.52%). Lupeol, stigmasterol and swertiamarin showed the interaction against the studied proteins viz., 1VSN, 5BNQ, 6HN8, 7DN4, 3TJU with varied energy values and interacting residues. The results of the virtual screening and molecular docking analysis suggest that the phytochemical compounds of <em>Cyathea</em> species viz., lupeol and stigmasterol were identified as possible lead molecules to fight against cancer and cytotoxicity.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100115"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49771435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA adducts as link between in vitro and in vivo carcinogenicity – A case study with benzo[a]pyrene","authors":"Martin Gerhards ,&nbsp;Alexander Böhme ,&nbsp;Kristin Schubert ,&nbsp;Bernhard Kodritsch ,&nbsp;Nadin Ulrich","doi":"10.1016/j.crtox.2022.100097","DOIUrl":"https://doi.org/10.1016/j.crtox.2022.100097","url":null,"abstract":"<div><p>To reduce the need for animal tests, <em>in vitro</em> assays are often used as alternative methods. To derive toxic doses for higher tier organisms from <em>in vitro</em> assay results, quantitative <em>in vitro-in vivo</em> extrapolation (qIVIVE) based on physiological-based toxicokinetic (PBTK) models is typically the preferred approach. Such PBTK models require many input parameters to address the route from dose to target site concentration. However, respective data is very often not available. Hence, our aim is to call attention to an alternative way to build a link between animal (<em>in vivo</em>) and cell-derived (<em>in vitro</em>) toxicity data. To this end, we selected the carcinogenic chemical benzo[<em>a</em>]pyrene (BaP) for our study. Our approach relates both <em>in vitro</em> assay and <em>in vivo</em> data to a main intermediate marker structure for carcinogenicity on the subcellular level – the BaP-DNA adduct BaP-7,8-dihydrodiol-9,10-epoxide-deoxyguanosine. Thus, BaP dose is directly linked to a measure of the toxicity-initiating event. We used Syrian hamster embryo (SHE) and Balb/c 3T3 cell transformation assay as <em>in vitro</em> data and compared these data to outcomes of <em>in vivo</em> carcinogenicity tests in rodents. <em>In vitro</em> and <em>in vivo</em> DNA adduct levels range within three orders of magnitude. Especially metabolic saturation at higher doses and interspecies variabilities are identified and critically discussed as possible sources of errors in our simplified approach. Finally, our study points out possible routes to overcome limitations of the envisaged approach in order to allow for a reliable qIVIVE in the future.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100097"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49777785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant activity of glucosamine and its effects on ROS production, Nrf2, and O-GlcNAc expression in HMEC-1 cells","authors":"B. Fernández-Rojas ,&nbsp;T. Gómez-Sierra ,&nbsp;O.N. Medina-Campos ,&nbsp;J. Hernández-Juárez ,&nbsp;P.A. Hernández-Cruz ,&nbsp;I.B. Gallegos-Velasco ,&nbsp;Y. Pérez-Cervera ,&nbsp;J. Pedraza-Chaverri","doi":"10.1016/j.crtox.2023.100128","DOIUrl":"10.1016/j.crtox.2023.100128","url":null,"abstract":"<div><p>Glucosamine (GlcN) is the most used supplement for osteoarthritis treatment. <em>In vitro</em> studies have related GlcN to beneficial and detrimental effects on health. The aim of this study was to evaluate the effects of O-linked-N-acetylglucosaminylation (O-GlcNAc) on GlcN-induced ROS production and Nrf2 expression in human dermal microvascular endothelial cells-1 (HMEC-1) and to evaluate the antioxidant capacity of GlcN compared to well-known antioxidants. For this, we evaluate the antioxidant capacity by <em>in vitro</em> assays. Besides, the GlcN (5–20 mM) effects on cell viability, reactive oxygen species (ROS) production, O-GlcNAc, and nuclear factor erythroid-2-related factor 2 (Nrf2) expression with and without the O-GlcNAc inhibitor OSMI-1 (10 μM) in HMEC-1 were evaluated. GlcN showed high inhibitory concentration (low scavenging activity) against superoxide (O₂^•─, IC₂₀ = 47.67 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH^•, IC₅₀ = 21.32 mM), and hydroxyl (HO^•, IC₅₀ = 14.04 mM) radicals without scavenging activity against hydrogen peroxide (H₂O₂) and low antioxidant capacity determined by oxygen radical absorbance capacity (ORAC, 0.001 mM Trolox equivalent) and ferric reducing antioxidant power (FRAP, 0.046 mM Trolox equivalent). In cell culture, GlcN (20 mM) reduced cell viability up to 26 % and induced an increase in ROS production (up to 70 %), O-GlcNAc (4-fold-higher <em>vs.</em> control), and Nrf2 expression (56 %), which were prevented by OSMI-1. These data suggest an association between O-GlcNAc, ROS production, and Nrf2 expression in HMEC-1 cells stimulated with GlcN.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100128"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/82/main.PMC10558709.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats","authors":"Chidinma P. Anyachor ,&nbsp;Chinna N. Orish ,&nbsp;Anthonet N. Ezejiofor ,&nbsp;Ana Cirovic ,&nbsp;Aleksandar Cirovic ,&nbsp;Kenneth M. Ezealisiji ,&nbsp;Orish E. Orisakwe","doi":"10.1016/j.crtox.2023.100129","DOIUrl":"10.1016/j.crtox.2023.100129","url":null,"abstract":"<div><p>This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, <em>cyclo</em>-oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p &lt; 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p &lt; 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100129"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross species extrapolation of the disruption of thyroid hormone synthesis by oxyfluorfen using in vitro data, physiologically based pharmacokinetic (PBPK), and thyroid hormone kinetics models","authors":"Rhylee Decrane ,&nbsp;Tammy Stoker ,&nbsp;Ashley Murr ,&nbsp;Jermaine Ford ,&nbsp;Hisham El-Masri","doi":"10.1016/j.crtox.2023.100138","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100138","url":null,"abstract":"<div><p>The thyroid hormones play key roles in physiological processes such as regulation of the metabolic and cardiac systems as well as the development of the brain and surrounding sympathetic nervous system. Recent efforts to screen environmental chemicals for their ability to alter thyroid hormone synthesis, transport, metabolism and/or function have identified novel chemicals that target key processes in the thyroid pathway. One newly identified chemical, oxyfluorfen, is a diphenyl-ether herbicide used for control of annual broadleaf and grassy weeds in a variety of tree fruit, nut, vine, and field crops. Using in vitro high-throughput screening (HTS) assays, oxyfluorofen was identified to be a potent inhibitor of the thyroidal sodium-iodide symporter (NIS). To quantitatively assess this inhibition mechanism in vivo, we extrapolated in vitro NIS inhibition data to in vivo disruption of thyroid hormones synthesis in rats using physiologically based pharmacokinetic (PBPK) and thyroid hormone kinetics models. The overall computational model (chemical PBPK and THs kinetic sub-models) was calibrated against in vivo data for the levels of oxyfluorfen in thyroid tissue and serum and against serum levels of thyroid hormones triiodothyronine (T3) and thyroxine (T4) in rats. The rat thyroid model was then extrapolated to humans using human in vitro HTS data for NIS inhibition and the chemical specific hepatic clearance rate in humans. The overall species extrapolated PBPK-thyroid kinetics model can be used to predict dose–response (% drop in thyroid serum levels compared to homeostasis) relationships in humans. These relationships can be used to estimate points of departure for health risks related to a drop in serum levels of TH hormones based on HTS assays in vitro to in vivo extrapolation (IVIVE), toxicokinetics, and physiological principles.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100138"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X23000361/pdfft?md5=7ca2681593829e2a02aa28ab79152521&pid=1-s2.0-S2666027X23000361-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confirmation of high-throughput screening data and novel mechanistic insights into FXR-xenobiotic interactions by orthogonal assays","authors":"Jon Hamm ,&nbsp;Debabrata Mahapatra ,&nbsp;Megan M. Knuth ,&nbsp;Jaleh Abedini ,&nbsp;Mary Lingerfelt ,&nbsp;Sean Ekins ,&nbsp;Seth W. Kullman","doi":"10.1016/j.crtox.2022.100092","DOIUrl":"10.1016/j.crtox.2022.100092","url":null,"abstract":"<div><p>Toxicology in the 21st Century (Tox21) is a federal collaboration employing a high-throughput robotic screening system to test 10,000 environmental chemicals. One of the primary goals of the program is prioritizing toxicity evaluations through <em>in vitro</em> high-throughput screening (HTS) assays for large numbers of chemicals already in commercial use for which little or no toxicity data is available. Within the Tox21 screening program, disruption in nuclear receptor (NR) signaling represents a particular area of interest. Given the role of NR’s in modulating a wide range of biological processes, alterations of their activity can have profound biological impacts. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that has demonstrated importance in bile acid homeostasis, glucose metabolism, lipid homeostasis and hepatic regeneration. In this study, we re-evaluated 24 FXR agonists and antagonists identified through Tox21 using select orthogonal assays. In transient transactivation assays, 7/8 putative agonists and 4/4 putative inactive compounds were confirmed. Likewise, we confirmed 9/12 antagonists tested. Using a mammalian two hybrid approach we demonstrate that both FXR agonists and antagonists facilitate FXRα-coregulator interactions suggesting that differential coregulator recruitment may mediate activation/repression of FXRα mediated transcription. Additionally, we tested the ability of select FXR agonists and antagonists to facilitate hepatic transcription of FXR gene targets Shp and Bsep in a teleost (Medaka) model. Through application of <em>in vitro</em> cell-based assays, <em>in silico</em> modeling and <em>in vivo</em> gene expressions, we demonstrated the molecular complexity of FXR:ligand interactions and confirmed the ability of diverse ligands to modulate FXRα, facilitate differential coregulator recruitment and activate/repress receptor-mediated transcription. Overall, we suggest a multiplicative approach to assessment of nuclear receptor function may facilitate a greater understanding of the biological and mechanistic complexities of nuclear receptor activities and further our ability to interpret broad HTS outcomes.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"3 ","pages":"Article 100092"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/4f/main.PMC9637864.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aflatoxin B1 targeted gene expression profiles in human placental primary trophoblast cells","authors":"Rami El-Dairi,&nbsp;Jaana Rysä,&nbsp;Markus Storvik,&nbsp;Markku Pasanen,&nbsp;Pasi Huuskonen","doi":"10.1016/j.crtox.2022.100082","DOIUrl":"10.1016/j.crtox.2022.100082","url":null,"abstract":"<div><p>Aflatoxin B1 (AFB1) is a mycotoxin produced by <em>Aspergillus flavus</em> and <em>A. parasiticus.</em> A high exposure (40 nM and 1 µM AFB1 for 72 h) was used to study mechanistic effects of AFB1 on gene expression patterns in human primary trophoblast cells, isolated from full term placentae after delivery. Gene expression profiling was conducted, and Ingenuity pathway analysis (IPA) software was used to identify AFB1-regulated gene networks and regulatory pathways.</p><p>In response to 40 nM AFB1, only 7 genes were differentially expressed whereas 1 µM AFB1 significantly dysregulated 170 genes (124 down- and 46 upregulated, ±1.5-fold, p &lt; 0.05) in AFB1-exposed trophoblasts when compared to controls. The top downregulated genes were involved in endocrine signalling and biosynthesis of hormones, and lipid and carbohydrate metabolism. The top upregulated genes were involved in protein synthesis and regulation of cell cycle. The main canonical pathways identified by IPA were associated with endocrine signalling including growth hormone signalling, and corticotropin releasing hormone signalling. Furthermore, genes involved in aryl hydrocarbon receptor (AhR)-mediated estrogen receptor signalling were dysregulated in response to AFB1.</p><p>Our findings indicate that a high concentration 72 h AFB1 exposure caused relatively moderate number of changes on transcript level to human placental primary trophoblast cells. However, these preliminary results need to be confirmed with human-relevant concentrations of AFB1.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"3 ","pages":"Article 100082"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/34/main.PMC9263407.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9181309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental deltamethrin: Sex-specific hippocampal effects in Sprague Dawley rats","authors":"Emily M. Pitzer ,&nbsp;Chiho Sugimoto ,&nbsp;Samantha L. Regan ,&nbsp;Gary A. Gudelsky ,&nbsp;Michael T. Williams ,&nbsp;Charles V. Vorhees","doi":"10.1016/j.crtox.2022.100093","DOIUrl":"10.1016/j.crtox.2022.100093","url":null,"abstract":"<div><p>Pyrethroid pesticides are widely used and can cause long-term effects after early exposure. Epidemiological and animal studies reveal associations between pyrethroid exposure and altered cognition following prenatal and/or neonatal exposure. However, little is known about the cellular effects of such exposure. Sprague Dawley rats were gavaged with 0 or 1.0 mg/kg deltamethrin (DLM), a Type II pyrethroid, in corn oil (dose volume 5 mL/kg) once per day from postnatal day (P) 3–20 and assessed shortly after dosing ended or as adults. No effects of DLM exposure were found on striatal dopaminergic markers, nor on AMPA receptor subunits or on NMDA-NR1. However, DLM increased NMDA-NR2A and decreased NMDA-NR2B levels in the hippocampus, in males but not females. Additionally, adult hippocampal CA1 long-term potentiation was increased in DLM-treated males but not females. Potassium stimulated extracellular glutamate release in the hippocampus was not affected using <em>in vivo</em> microdialysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed increased apoptotic cells in the dentate gyrus of male rats, in the absence of changes in cleaved caspase-3 at P21. Proinflammatory cytokines interferon gamma trended up in striatum, interleukin-1β trended down in nucleus accumbens, IL-13 trended up in hippocampus, and keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO or CXCL1) was significantly increased in the hippocampus in male DLM-treated rats on P20. The data point to the developing hippocampus as a susceptible region to DLM-induced adverse effects.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9661443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9200966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Comments on the paper of Wylie and Korchevskiy – Carcinogenicity of fibrous glaucophane: How should we fill the data gaps?","authors":"Alessandro F. Gualtieri,&nbsp;Dario Di Giuseppe","doi":"10.1016/j.crtox.2021.100063","DOIUrl":"10.1016/j.crtox.2021.100063","url":null,"abstract":"<div><p>Assessing the human health risk of mineral fibres is an intricate task. In the recent article by Wylie and Korchevskiy (2021) – Carcinogenicity of fibrous glaucophane: how to fill data gaps? (Curr. Res. Toxicol. Vol. 2, pp. 202–203), the authors discuss the potential toxicity and pathogenicity of fibrous glaucophane from the Franciscan Complex, California (USA). Because most of the points of discussion concerns the mineral fibre toxicity/pathogenicity model developed by our research group and the application to the case of fibrous glaucophane (Gualtieri, 2021, Curr. Res. Toxicol. Vol. 2, pp. 42–52), the aim of this Letter is to clear some basic issues, to fill some information gaps and, with a constructive spirit, to provide a complete picture on this topic.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"3 ","pages":"Article 100063"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/cd/main.PMC8762068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39855561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}