Notch1-Mediated Histone Demethylation of HCN4 Contributes to Aconitine-induced Ventricular Myocardial Dysrhythmia.
Abstract Traditional Chinese Medicines (TCMs)-containing aconitine are popular and indispensable home remedies in Asia for thousands of years due to its excellent pharmaceutical effects. Accumulating evidence has identified that repeated-dose of aconitine could cause polymorphic ventricular arrhythmias. However, underlying molecular mechanisms are still not fully understood. Hence, the present study firstly investigated the potential role of Notch1 signaling in aconitine-induced cardiotoxicity, aiming to elaborate possible molecular mechanisms involved in aconitine triggered ventricular arrhythmias. Our results sh...
Source: Toxicology Letters - March 28, 2020 Category: Toxicology Authors: Zhou W, Qiu LZ, Liu H, Deng HF, Yue LX, Gao Y Tags: Toxicol Lett Source Type: research

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate.
Abstract In the field of engineered nanomaterials (ENMs) and other airborne particulate exposure biomonitoring, circulating oxidative stress biomarkers appear promising. These biomarkers could be monitored in different biological matrices. Exhaled breath condensate (EBC) enables their measurements in the respiratory tract, without affecting airway function or creating inflammation. The 8-hydroxy-2-deoxyguanosine (8-OHdG) was found increased in the EBC of ENM-exposed workers. Our objectives were to assess the reference range of 8-OHdG in the EBC and to identify determinants of its inter- and intra-individual variab...
Source: Toxicology Letters - March 28, 2020 Category: Toxicology Authors: Hemmendinger M, Wild P, Shoman Y, Graille M, Bergamaschi E, Hopf N, Guseva Canu I Tags: Toxicol Lett Source Type: research

Response to comment on 'Comparison of the toxic mechanism of T-2 toxin and deoxynivalenol on human chondrocytes by microarray and bioinformatics analysis'.
PMID: 32220604 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - March 24, 2020 Category: Toxicology Authors: Yang L, Guo X Tags: Toxicol Lett Source Type: research

An in vitro investigation into the protective and genotoxic effects of myricetin bulk and nano forms in lymphocytes of MGUS patients and healthy individuals.
Abstract The present study investigated the genoprotective and genotoxic effects of myricetin bulk (10 µM) and nano forms (20 µM) in the lymphocytes from pre-cancerous, monoclonal gammopathy of unknown significance (MGUS) patients and healthy individuals using the Comet and micronucleus assays. The study also evaluated the effect of myricetin on P53 expression levels, using the Western blot technique. Results showed that throughout the in-vitro treatment, lymphocytes from the patients group had higher levels of baseline DNA damage compared to the healthy group. Myricetin in both forms ind...
Source: Toxicology Letters - March 24, 2020 Category: Toxicology Authors: Akhtar S, Najafzadeh M, Isreb M, Newton L, Gopalan RC, Anderson D Tags: Toxicol Lett Source Type: research

Comment on 'Comparison of the toxic mechanism of T-2 toxin and deoxynivalenol on human chondrocytes by microarray and bioinformatics analysis'.
PMID: 32217143 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - March 23, 2020 Category: Toxicology Authors: Yang C, Li H, Cao C, Xu Y Tags: Toxicol Lett Source Type: research

SOD2 promotes the expression of ABCC2 through lncRNA CLCA3p and improves the detoxification capability of liver cells.
This study elucidates the improvement of the detoxification of liver cells by a regulatory axis, SOD2-CLCA3P-IRF1-ABCC2, and provides novel insight into the modification of human liver cells that can be applied to bioartificial liver system or the study of SOD2 in drug metabolism. PMID: 32201199 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - March 19, 2020 Category: Toxicology Authors: Wang X, Li M, Peng L, Tang N Tags: Toxicol Lett Source Type: research

Downregulation of vdac2 inhibits spermatogenesis via JNK and P53 signalling in mice exposed to cadmium.
In this study, mouse Leydig TM3 cells were treated with CdCl2 (0, 5, 10 and 50 μM) for 24 h to evaluate cytotoxicity, and C57BL/6 mice were treated intragastrically with 0.4 mL CdCl2 (0, 0.01, 0.05 and 0.1 g/L) for 2 months to investigate changes in spermatogenesis. The results showed that Cd aggravated apoptosis and proliferation in a dose-dependent manner, concomitant with deteriorated spermatogenesis and testosterone synthesis. For mechanism exploration, RNA-seq was used to profile alterations in gene expression in response to Cd, and the results indicated focus on P53/JNK signalling pathw...
Source: Toxicology Letters - March 18, 2020 Category: Toxicology Authors: Fang Y, Zhang L, Dong X, Wang H, He L, Zhong S Tags: Toxicol Lett Source Type: research

Trimeresurus albolabris snakebite treatment implications arising from ontogenetic venom comparisons of anticoagulant function, and antivenom efficacy.
Abstract Does the venom of Trimeresurus albolabris (white-lipped green tree pit viper) differ between neonate and adults? This species is responsible for most snakebites within south and southeast Asia, yet it is unknown whether ontogenetic variation in venom composition occurs in this species, or how this might affect antivenom efficacy. Using a coagulation analyser robot, we examined the anticoagulant activity of T. albolabris venom from eight individuals across multiple age classes. We then compared the efficacy of Thai Red Cross Green Tree Pit Viper Antivenom across these age classes. Venoms from all age class...
Source: Toxicology Letters - March 18, 2020 Category: Toxicology Authors: Bourke LA, Youngman NJ, Zdenek CN, Op den Brouw B, Violette A, Fourmy R, Fry BG Tags: Toxicol Lett Source Type: research

Comparative genotoxic potential of 27 polycyclic aromatic hydrocarbons in three human cell lines.
Abstract Polycyclic Aromatic Hydrocarbons (PAHs) form a family of compounds that are generally found in complex mixtures. PAHs can lead to the development of carcinogenesis. The Toxicity Equivalent Factor (TEF) approach has been suggested for estimating the toxicity of PAHs, however, due to the relative weakness of available data, TEF have not been applied for the risk characterization of PAHs as food contaminants in Europe. The determination of new TEFs for a large number of PAHs could overcome some limitations of the current method and improve cancer risk assessment. The present investigation aimed at deriving n...
Source: Toxicology Letters - March 14, 2020 Category: Toxicology Authors: Tomasetig F, Tebby C, Graillot V, Zeman F, Pery A, Cravedi JP, Audebert M Tags: Toxicol Lett Source Type: research

DNA damage signaling in the cellular responses to mustard vesicants.
Abstract Mustard vesicants, including sulfur mustard (2,2'-dichlorodiethyl sulfide, SM) and nitrogen mustard (bis(2-chloroethyl)methylamine, HN2) are cytotoxic blistering agents synthesized for chemical warfare. Because they contain highly reactive electrophilic chloroethyl side chains, they readily react with cellular macromolecules like DNA forming monofunctional and bifunctional adducts. By targeting DNA, mustards can compromise genomic integrity, disrupt the cell cycle, and cause mutations and cytotoxicity. To protect against genotoxicity following exposure to mustards, cells initiate a DNA damage response (DD...
Source: Toxicology Letters - March 12, 2020 Category: Toxicology Authors: Jan YH, Heck DE, Laskin DL, Laskin JD Tags: Toxicol Lett Source Type: research

Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke.
In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells. PMID: 32169443 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - March 10, 2020 Category: Toxicology Authors: Di Sano C, D'Anna C, Ferraro M, Chiappara G, Sangiorgi C, Di Vincenzo S, Bertani A, Vitulo P, Bruno A, Dino P, Pace E Tags: Toxicol Lett Source Type: research

N-(2-Hydroxyethyl)-L-valyl-L-leucine: a novel urinary biomarker of ethylene oxide exposure in humans.
Š, Tvrdíková M, Linhart I Abstract Ethylene oxide (EO), a carcinogenic chemical used as an industrial intermediate and sterilant, forms covalent adducts with DNA and proteins. The adduct with N-terminal valine [N-(2-hydroxyethyl)-L-valine, HEV] in blood protein globin has been employed as a principal biomarker of cumulative exposures to EO. However, as sampling of blood is inconvenient in routine occupational health practice, a non-invasive alternative to globin analysis has been investigated. Following identification of N-(2-hydroxyethyl)-L-valyl-L-leucine (HEVL) as ultimate cleavage product...
Source: Toxicology Letters - March 4, 2020 Category: Toxicology Authors: Mráz J, Hanzlíková I, Dušková Š, Tvrdíková M, Linhart I Tags: Toxicol Lett Source Type: research

Pesticides, cognitive functions and dementia: A review.
Abstract Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the a...
Source: Toxicology Letters - March 4, 2020 Category: Toxicology Authors: Aloizou AM, Siokas V, Vogiatzi C, Peristeri E, Docea A, Petrakis D, Provatas A, Folia V, Chalkia C, Vinceti M, Wilks M, Izotov BN, Tsatsakis A, Bogdanos DP, Dardiotis E Tags: Toxicol Lett Source Type: research

NIX compensates lost role of Parkin in Cd-induced mitophagy in HeLa cells through phosphorylation.
Abstract Our previous study demonstrated that cadmium (Cd) is an effective inducer of mitophagy, which is mainly mediated by PINK1/Parkin pathway. However, the role of other mitophagy pathways in Cd-induced mitophagy remains elusive. The present study employed HeLa cells, lacking fully functional Parkin, as a cell model to study Parkin-independent mitophagy pathway induced by Cd. Our results showed that BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (Bnip3L/NIX), an outer mitochondrial membrane mitophagy receptor, could provide an alternate pathway for Cd-induced mitophagy in HeLa cells. Spec...
Source: Toxicology Letters - March 3, 2020 Category: Toxicology Authors: Naeem S, Qi Y, Tian Y, Zhang Y Tags: Toxicol Lett Source Type: research

Arsenite-induced Transgenerational Glycometabolism is Associated with Up-regulation of H3K4me2 via Inhibiting spr-5 in Caenorhabditis Elegans.
This study highlights that single generation exposure to arsenite causes transgenerational changes in glycometabolism in C. elegans, which may be caused by downregulation of spr-5 and elevation of H3K4me2. PMID: 32142838 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - March 3, 2020 Category: Toxicology Authors: Gu C, Wen Y, Wu L, Wang Y, Wu Q, Wang D, Wang Y, Liu Q, Zhang J Tags: Toxicol Lett Source Type: research

Microcystin-LR Impairs Glucose Metabolism in Pancreatic β Cells in Vivo and in Vitro.
This study aimed to investigate the toxic effects of microcystin-LR (MC-LR), which is released from several bloom-forming cyanobacteria, on the glucose metabolism of pancreatic β cells in vivo and in vitro. Male mice and the pancreatic MIN6 cells were respectively treated with varying concentrations of MC-LR. After 3- or 6- months of MC-LR exposure, increase in the body weight of mice was found to be inhibited, and the structure of their pancreatic tissues was damaged with impaired glucose tolerance and impaired insulin secretion. Further, these toxic effects became more pronounced with time and with increased dosages...
Source: Toxicology Letters - March 3, 2020 Category: Toxicology Authors: Chen Y, Chen K, Zhou Y, Li X, Mao X, Wei X, Xu Y, Yang W, Chen G, Liu C Tags: Toxicol Lett Source Type: research

Evaluation of the epigenetic alterations and gene expression levels of HepG2 cells exposed to zearalenone and α-zearalenol.
Evaluation of the epigenetic alterations and gene expression levels of HepG2 cells exposed to zearalenone and α-zearalenol. Toxicol Lett. 2020 Feb 28;: Authors: Karaman EF, Zeybel M, Ozden S Abstract Zearalenone, produced by various Fusarium species, is a non-steroidal estrogenic mycotoxin that contaminates cereals, resulting in adverse effects on human health. We investigated the effects of zearalenone and its metabolite alpha zearalenol on epigenetic modifications and its relationship with metabolic pathways in human hepatocellular carcinoma cells following 24 h of exposure. Zearalenone...
Source: Toxicology Letters - February 28, 2020 Category: Toxicology Authors: Karaman EF, Zeybel M, Ozden S Tags: Toxicol Lett Source Type: research

Activities of metabolizing enzymes in human placenta.
ACTIVITIES OF METABOLIZING ENZYMES IN HUMAN PLACENTA. Toxicol Lett. 2020 Feb 27;: Authors: Mohammed AM, Huuskonen P, Juvonen R, Sahlman H, Repo J, Myöhänen K, Myllynen P, Woo CJ, Karttunen V, Vähäkangas K Abstract In addition to the transfer across the placenta, placenta displays hormonal and xenobiotic metabolism, as well as enzymatic defense against oxidative stress. We analyzed aromatase (CYP19A1), uridine 5'-diphospho-glucuronyltransferase (UGT), glutathione-S-transferase (GST) and catalase (CAT) activitiesin over 70 placentas from nonsmokers stored at -80 °C from fo...
Source: Toxicology Letters - February 27, 2020 Category: Toxicology Authors: Mohammed AM, Huuskonen P, Juvonen R, Sahlman H, Repo J, Myöhänen K, Myllynen P, Woo CJ, Karttunen V, Vähäkangas K Tags: Toxicol Lett Source Type: research

Airway basal cell injury after acute diacetyl (2,3-butanedione) vapor exposure.
CONCLUSIONS: Diacetyl exposure results in airway basal cell injury with keratin 5 ubiquitination and decreased p63 expression. The ubiquitin-proteasome-pathway partially mediates airway basal cell repair after acute DA exposure. PMID: 32112875 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - February 26, 2020 Category: Toxicology Authors: McGraw MD, Kim SY, Reed C, Hernady E, Rahman I, Mariani TJ, Finkelstein JN Tags: Toxicol Lett Source Type: research

Arsenic-induced Autophagic Alterations and Mitochondrial Impairments in HPG-S Axis of Mature Male Mice Offspring (F1-generation): A persistent toxicity study.
Abstract Arsenic (As) has been implicated in causing reproductive toxicity, but the precise cellular pathway through which the As toxicity in mature F1- male mice hypothalamic-pituitary- gonadal- sperm (HPG-S) axis is induced has not well been documented. Hence, parental mice were treated to As2O3 (0, 0.2, 2, and 20 ppm in deionized water) from five weeks before mating until weaning, and the male pups from weaning to maturity. Afterward, the markers of oxidative stress, mitochondrial impairment, and autophagy as fundamental mechanisms of cytotoxicity and organ injury were evaluated. Higher As2O3 doses (2 an...
Source: Toxicology Letters - February 26, 2020 Category: Toxicology Authors: Ommati MM, Manthari RK, Tikka C, Niu R, Sun Z, Sabouri S, Zamiri MJ, Ahmadi HN, Ghaffari H, Heidari R, Wang J Tags: Toxicol Lett Source Type: research

Dose-response analysis of toxicological and pharmacological mixtures with the model deviation ratio method: problems and solutions.
Abstract Risk assessment for mixtures of chemicals requires to investigate the magnitude of their potential adverse effects on living organisms. This is usually done by assessing how experimental toxicological mixture data depart from the model of Loewe additivity. Several recent scientific studies propose to perform this task using an ad hoc method known as Model Deviation Ratio (MDR) method. Moreover, the first official European regulatory document for the study of combined exposures explicitly recommends the use of the MDR method (EFSA Scientific Committee et al. Guidance on harmonised methodologies for human h...
Source: Toxicology Letters - February 25, 2020 Category: Toxicology Authors: Macacu A, Lasagni S, Carnesecchi E, Dorne JL, Guillot G Tags: Toxicol Lett Source Type: research

A reporter cell line for real-time imaging of autophagy and apoptosis.
Abstract Simultaneous detection of autophagy and apoptosis is important in drug discovery and signaling studies. Here we report, a real-time reporter cell line for the simultaneous detection of apoptosis and autophagy at single-cell level employing stable integration of two fluorescent protein reporters of apoptosis and autophagy. Cells stably expressing EGFP-LC3 fusion was developed initially as a marker for autophagy and subsequently stably expressed with inter-mitochondrial membrane protein SMAC with RFP fusion to detect mitochondrial permeabilization event of apoptosis. The cell lines faithfully reported the L...
Source: Toxicology Letters - February 25, 2020 Category: Toxicology Authors: Lupitha SS, Chandrasekhar L, Varadarajan SN, Jayaprasad AG, Chandrasekharan A, Patil SN, Mini M, Pillai PR, Santhoshkumar TR Tags: Toxicol Lett Source Type: research

Mass spectrometry imaging reveals lipid upregulation and bile acid changes indicating amitriptyline induced steatosis in a rat model.
In this study, Amitriptyline treated male rat liver tissue was analyzed using Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging (MALDI-MSI) to investigate the spatial abundances of Amitriptyline, lipids, and bile acids. The metabolism of Amitriptyline in liver tissue was successfully demonstrated, as the spatial distribution of Amitriptyline and its metabolites localize throughout treatment group liver samples. Several lipids appear upregulated, from which nine were identified as distinct phosphatidylcholine (PC) species. The detected bile acids were found to be lower in Amitriptyline treatment group. T...
Source: Toxicology Letters - February 21, 2020 Category: Toxicology Authors: Kampa JM, Sahin M, Slopianka M, Giampà M, Bednarz H, Ernst R, Riefke B, Niehaus K, Fatangare A Tags: Toxicol Lett Source Type: research

Differential activation of human pregnane X receptor PXR by isomeric mono-methylated indoles in intestinal and hepatic in vitro models.
i H, Mani S, Dvořák Z Abstract Dietary and microbial indoles can act as ligands and activators of pregnane X receptor (PXR), with implications in human intestinal health. In the current study, we examined the effects of simple mono-methylated indoles (MMIs) on the activity and function of PXR, using a series of human hepatic and intestinal cell models. Indoles 1-MMI and 2-MMI strongly induced CYP3A4 and MDR1 mRNAs in human intestinal adenocarcinoma cells LS180, but not in primary human hepatocytes. The levels of CYP3A4 mRNA were increased by 1-MMI and 2-MMI in wild type, but not in PXR-knock-out human hepa...
Source: Toxicology Letters - February 21, 2020 Category: Toxicology Authors: Vyhlídalová B, Bartoňková I, Jiskrová E, Li H, Mani S, Dvořák Z Tags: Toxicol Lett Source Type: research

Drp1, a potential therapeutic target for Parkinson's disease, is involved in olfactory bulb pathological alteration in the Rotenone-induced rat model.
This study was designed to investigate the relationship between olfactory bulb and inflammatory pathological alterations and the potential mechanisms. Here we found that rotenone led to typical parkinsonian symptoms and decreased tyrosine hydroxylase (TH)-positive neurons in the olfactory bulb. Additionally, increased NF-κB nuclear translocation and NLRP3 inflammasome components expressions caused by rotenone injection were observed accompanied by the activation of microglia and astrocytes in the olfactory bulb. Rotenone also triggered Drp1-mediated mitochondrial fission and this in turn caused mitochondrial damage. ...
Source: Toxicology Letters - February 20, 2020 Category: Toxicology Authors: Zhang X, Huang W, Shao Q, Yang Y, Xu Z, Chen J, Zhang X, Ge X Tags: Toxicol Lett Source Type: research

Carfentanil Toxicity in the African Green Monkey: Therapeutic Efficacy of Naloxone.
Abstract Carfentanil is an ultra-potent opioid with an analgesic potency 10,000 times that of morphine but has received little scientific investigation. Three experiments were conducted to evaluate the toxicity of carfentanil and the efficacy of naloxone in adult male African green monkeys. The first experiment determined the ED50 (found to be 0.71 µg/kg) of subcutaneous carfentanil for inducing bradypnea and/or loss of posture. Experiment 2 attempted to establish the ED50 of naloxone for rapidly reversing the bradypnea/loss of posture induced by carfentanil (1.15 µg/kg). Experiment 3 eva...
Source: Toxicology Letters - February 15, 2020 Category: Toxicology Authors: Langston JL, Moffett MC, Makar JR, Burgan BM, Myers TM Tags: Toxicol Lett Source Type: research

Soluble silver ions from silver nanoparticles induce a polarised secretion of interleukin-8 in differentiated Caco-2 cells.
Abstract Because of their antimicrobial properties, silver nanoparticles are increasingly incorporated in food-related and hygiene products, which thereby could lead to their ingestion. Although their cytotoxicity mediated by oxidative stress has been largely studied, their effects on inflammation remain controversial. Moreover, the involvement of silver ions (originating from Ag0 oxidation) in their mode of action is still unclear. In this context, the present study aims at assessing the impact of silver nanoparticles on the secretion of the pro-inflammatory chemokine interleukin-8 by Caco-2 cells forming an in v...
Source: Toxicology Letters - February 13, 2020 Category: Toxicology Authors: Polet M, Laloux L, Cambier S, Ziebel J, Gutleb AC, Schneider YJ Tags: Toxicol Lett Source Type: research

Tolylfluanid permeates human skin slowly and as dimethylamino sulfotoluidid (DMST).
Abstract Tolylfluanid (TF) is a sensitizing biocide used in antifouling products and wood preservatives. Paint application is associated with skin exposure; however, the importance of this exposure route is uncertain as TF skin permeation rates are lacking in the peer-reviewed scientific literature. TF is a lipophilic powder that hydrolyses rapidly in contact with water to dimethylamino sulfotoluidid (DMST). DMST is also a TF metabolite. We characterized TF and DMST skin permeation using an ex vivo flow-through diffusion system with viable and frozen human skin. TF permeated as DMST with a low permeation rate (0.1...
Source: Toxicology Letters - February 13, 2020 Category: Toxicology Authors: Berthet A, Hechon J, Hopf NB Tags: Toxicol Lett Source Type: research

Dried blood microsamples: suitable as an alternative matrix for the quantification of paracetamol-protein adducts?
Abstract Paracetamol (acetaminophen, APAP) is the most frequently used analgesic drug worldwide. However, patients in several specific populations can have an increased exposure to toxic APAP metabolites. Therefore, APAP-protein adducts have been proposed as an alternative marker for the assessment of APAP intoxications and as an effective tool to study and steer APAP treatment in patients with an increased risk of APAP-induced liver damage. These adducts have been determined in plasma or serum as a matrix. Blood microsampling allows the determination of a variety of analytes, including protein adducts, in a drop ...
Source: Toxicology Letters - February 6, 2020 Category: Toxicology Authors: Delahaye L, Dhont E, De Cock P, De Paepe P, Stove CP Tags: Toxicol Lett Source Type: research

DNA damage in colon mucosa of Pirc rats, an Apc-driven model of colon tumorigenesis.
Abstract APC mutation is the first event triggering colon carcinogenesis (CRC). The contribution of APC to colon mucosa DNA damage is not well characterized yet. Similarly, the role of genotoxin-producer gut microorganisms is unclear. DNA strand breaks and oxidative damage were measured in Pirc rats, mutated in Apc, with the COMET assay at 1 (T1) and 11 months (T11), i.e. in absence and presence of colon adenomas. In Pirc colon mucosa a 2-fold increase in the mean level of DNA oxidative damage was found at T11 compared to T1. Moreover, the analysis of DNA damage distribution showed that the proportion of Pirc muco...
Source: Toxicology Letters - February 6, 2020 Category: Toxicology Authors: Tortora K, Vitali F, De Filippo C, Caderni G, Giovannelli L Tags: Toxicol Lett Source Type: research

α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish.
This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 μM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased hear...
Source: Toxicology Letters - February 5, 2020 Category: Toxicology Authors: Shang X, Ji X, Dang J, Wang L, Sun C, Liu K, Sik A, Jin M Tags: Toxicol Lett Source Type: research

NAD+ in sulfur mustard toxicity.
h A Abstract Sulfur mustard (SM) is a toxicant and chemical warfare agent with strong vesicant properties. The mechanisms behind SM-induced toxicity are not fully understood and no antidote or effective therapy against SM exists. Both, the risk of SM release in asymmetric conflicts or terrorist attacks and the usage of SM-derived nitrogen mustards as cancer chemotherapeutics, render the mechanisms of mustard-induced toxicity a highly relevant research subject. Herein, we review a central role of the abundant cellular molecule nicotinamide adenine dinucleotide (NAD+) in molecular mechanisms underlying SM toxicity. ...
Source: Toxicology Letters - February 1, 2020 Category: Toxicology Authors: Ruszkiewicz JA, Bürkle A, Mangerich A Tags: Toxicol Lett Source Type: research

Classification, hepatotoxic mechanisms, and targets of the risk ingredients in traditional Chinese medicine-induced liver injury.
Abstract Traditional Chinese medicine (TCM) has become a crucial cause of drug-induced liver injury (DILI). Differ from chemical medicines, TCM feature more complex and mostly indefinite components. This review aimed to clarify the classification, underlying mechanisms and targets of the risk components in TCM-induced liver injury to further guide the secure application of TCM. Relevant studies or articles published on the PubMed database from January 2008 to December 2019 were searched. Based on the different chemical structures of the risk ingredients in TCM, they are divided into alkaloids, glycosides, toxic pr...
Source: Toxicology Letters - February 1, 2020 Category: Toxicology Authors: Pan X, Zhou J, Chen Y, Xie X, Rao C, Liang J, Zhang Y, Peng C Tags: Toxicol Lett Source Type: research

Overexpression of endogenous lipoic acid synthase attenuates pulmonary fibrosis induced by crystalline silica in mice.
Abstract Oxidative stress and inflammatory processes are proposed to mediate the development of silicosis. However, antioxidant therapy has not produced consistent results during the treatment of silicosis. α-Lipoic acid synthesized by lipoic acid synthase is a powerful anti-oxidant and helps protect mitochondria. Thus far, the effect of endogenous α-Lipoic acid on silicosis has not been elucidated yet. We established an experimental model of silicosis with wildtype and LiasH/H mice, a new antioxidant mouse model which has overexpressed Lias gene (∼150%) relative to its wild type counterpart. We sy...
Source: Toxicology Letters - February 1, 2020 Category: Toxicology Authors: Zhao Y, Xu G, Li H, Chang M, Guan Y, Li Y, Wu W, Yao S Tags: Toxicol Lett Source Type: research

3-Quinuclidinyl- α-methoxydiphenylacetate: a multi-targeted ligand with antimuscarinic and antinicotinic effects designed for the treatment of anticholinesterase poisoning.
3-Quinuclidinyl-α-methoxydiphenylacetate: a multi-targeted ligand with antimuscarinic and antinicotinic effects designed for the treatment of anticholinesterase poisoning. Toxicol Lett. 2020 Feb 01;: Authors: Timperley CM, Bird M, Gore SJ, Lindsay CD, Rice H, Tattersall JEH, Whitmore CL, Green AC Abstract Racemic 3-quinuclidinyl-α-methoxydiphenylacetate (MB266) was synthesised. Its activity at muscarinic acetylcholine receptors (mAChRs), and muscle and neuronal nicotinic acetylcholine receptors (nAChRs), was compared to that of atropine and racemic 3-quinucidinyl benzilate (QNB) using a fu...
Source: Toxicology Letters - February 1, 2020 Category: Toxicology Authors: Timperley CM, Bird M, Gore SJ, Lindsay CD, Rice H, Tattersall JEH, Whitmore CL, Green AC Tags: Toxicol Lett Source Type: research

Towards a recommended biomonitoring strategy for assessing the occupational exposure of roofers to pahs.
TOWARDS A RECOMMENDED BIOMONITORING STRATEGY FOR ASSESSING THE OCCUPATIONAL EXPOSURE OF ROOFERS TO PAHS. Toxicol Lett. 2020 Jan 30;: Authors: Persoons R, Roseau L, Petit P, Hograindleur C, Montlevier S, Marques M, Ottoni G, Maitre A Abstract The aims of this work were to assess the PAH exposure among, roofers and to identify relevant biomarkers for monitoring occupational,exposure. Several campaigns were conducted between 2004 and 2017, with 28,individual air samples and 240 urinary samples collected from 73 roofers. Seventeen parent PAHs and 14 urinary biomarkers, metabolites of pyrene (1-OHP), benzo...
Source: Toxicology Letters - January 30, 2020 Category: Toxicology Authors: Persoons R, Roseau L, Petit P, Hograindleur C, Montlevier S, Marques M, Ottoni G, Maitre A Tags: Toxicol Lett Source Type: research

Adverse health effects of 5g mobile networking technology under real-life conditions.
This article identifies adverse effects of non-ionizing non-visible radiation (hereafter called wireless radiation) reported in the premier biomedical literature. It emphasizes that most of the laboratory experiments conducted to date are not designed to identify the more severe adverse effects reflective of the real-life operating environment in which wireless radiation systems operate. Many experiments do not include pulsing and modulation of the carrier signal. The vast majority do not account for synergistic adverse effects of other toxic stimuli (such as chemical and biological) acting in concert with the wireless rad...
Source: Toxicology Letters - January 25, 2020 Category: Toxicology Authors: Kostoff RN, Heroux P, Aschner M, Tsatsakis A Tags: Toxicol Lett Source Type: research

Endoplasmic reticulum stress, an important factor in the development of Parkinson's disease.
Abstract Similar to other types of neuronal degeneration, Parkinson's disease (PD) is characterized by the aggregation of a pathological protein, α-synuclein. The endoplasmic reticulum (ER) is the principal site of protein synthesis, quality control and degradation. Genetic mutants, environmental insults and other factors disturb ER balance and induce the accumulation of misfolded/unfolded proteins, which initiate ER stress and disturb normal cell function. ER stress perturbs Ca2+ homeostasis and initiates the activation of autophagy and inflammasomes, which have been identified as risk factors for the devel...
Source: Toxicology Letters - January 24, 2020 Category: Toxicology Authors: Mou Z, Yuan YH, Zhang Z, Song LK, Chen NH Tags: Toxicol Lett Source Type: research

The long persistence of pyrrolizidine alkaloid-derived pyrrole-protein adducts in vivo: Kinetic study following multiple exposures of a pyrrolizidine alkaloid containing extract of Gynura japonica.
Abstract Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb in...
Source: Toxicology Letters - January 23, 2020 Category: Toxicology Authors: Chen Y, Xiong F, Wang W, Jiang K, Ye X, Deng G, Wang C, Yang L, Xiong A, Wang Z Tags: Toxicol Lett Source Type: research

Chloropicrin-induced toxicity in the respiratory system.
angas K Abstract Chloropicrin is a volatile and reactive chemical that has been utilized as a warfare agent and a pesticide to fumigate soil against insects, fungi and nematodes. It poses a health risk to humans and animals if inhaled. The main source of chloropicrin exposure is occupational and occurs during its manufacture, transport and fumigation. Chloropicrin is toxic via all routes of exposure but the main route of systemic exposure is inhalation of the ambient air. Thus, the toxicity mainly affects the respiratory system. After a low level exposure, the first sign is irritation of the upper respiratory trac...
Source: Toxicology Letters - January 23, 2020 Category: Toxicology Authors: Pesonen M, Vähäkangas K Tags: Toxicol Lett Source Type: research

ZEA-induced autophagy in TM4 cells was mediated by the release of Ca2+ activates CaMKK β-AMPK signaling pathway in the endoplasmic reticulum.
ZEA-induced autophagy in TM4 cells was mediated by the release of Ca2+ activates CaMKKβ-AMPK signaling pathway in the endoplasmic reticulum. Toxicol Lett. 2020 Jan 23;: Authors: Feng N, Wang B, Cai P, Zheng W, Zou H, Gu J, Yuan Y, Liu X, Liu Z, Bian J Abstract Zearalenone (ZEA) is a prevalent non-steroidal estrogenic mycotoxin produced mainly by Fusarium contamination. Our previous study showed that ZEA induces the autophagy of Sertoli cells (SCs). However, the underlying mechanisms are still unknown. Several studies have indicated that the increasing level of cytoplasmic Ca2+ could induce autoph...
Source: Toxicology Letters - January 23, 2020 Category: Toxicology Authors: Feng N, Wang B, Cai P, Zheng W, Zou H, Gu J, Yuan Y, Liu X, Liu Z, Bian J Tags: Toxicol Lett Source Type: research

International landscape of limits and recommendations for occupational exposure to engineered nanomaterials.
ro NL, Chirino YI Abstract The increasing concern of possible adverse effects on human health derived from occupational engineered nanomaterials (ENMs) exposure is an issue addressed by entities related to provide guidelines and/or protocols for ENMs regulation. Here we analysed 17 entities from America, Europe and Asia, and some of these entities provide limits of exposure extrapolated from the non-nanosized counterparts of ENMs. The international landscape shows that recommendations are mostly made for metal oxide based ENMs and tonnage is one of the main criteria for ENMs registration, however, sub-nanometric E...
Source: Toxicology Letters - January 22, 2020 Category: Toxicology Authors: Rodríguez-Ibarra C, Déciga-Alcaraz A, Ispanixtlahuatl-Meráz O, Medina-Reyes EI, Delgado-Buenrostro NL, Chirino YI Tags: Toxicol Lett Source Type: research

Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin.
Abstract Isoniazid and rifampicin are well-known anti-mycobacterial agents and are widely used to treat pulmonary tuberculosis (TB) as part of the combined therapy approach, recommended by the World Health Organization. The ingestion of these first-line TB drugs are, however, not free of side-effects, and are toxic to the liver, kidney, and central nervous system. These side effects are associated with poor treatment compliance, resulting in TB treatment failure, relapse and drug resistant TB. This occurrence has subsequently led to the recent application of novel research technologies, towards a better understand...
Source: Toxicology Letters - January 22, 2020 Category: Toxicology Authors: Combrink M, Loots DT, du Preez I Tags: Toxicol Lett Source Type: research

Differences in Biological Activities between Recombinant Human Paraoxonase 1 (rhPON1) Subtype Isozemys R/Q as Antidotes against Organophosphrus Poisoning.
In this study, we obtained two subtype isozymes of recombinant human PON1 (rhPON1), which have gene polymorphisms in 192 locis, by gene recombination. We then investigated the differences between these two recombinant isozymes (i.e. rhPON1R192 and rhPON1Q192) in their detoxification effect against organophosphorus pesticide poisoning in rats. As antidotes against chlorpyrifos poisoning, the rhPON1R192 isozyme demonstrated better effect than the rhPON1Q192 isozyme; whereas, their detoxification activities against diazinon were on the contrary. Both isozymes showed poor detoxification activity against trithion. Therefore, we...
Source: Toxicology Letters - January 22, 2020 Category: Toxicology Authors: Cui Y, Zhao M, Han L Tags: Toxicol Lett Source Type: research

N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo model.
In conclusion, Cl2 induced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl2-induced lung injuries. PMID: 31962155 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - January 18, 2020 Category: Toxicology Authors: Ågren L, Elfsmark L, Akfur C, Hägglund L, Ekstrand-Hammarström B, Jonasson S Tags: Toxicol Lett Source Type: research

Acetoacetate Enhances Oxidative Metabolism and Response to Toxicants of Cultured Kidney Cells.
This study is designed to test the impact of the ketone body acetoacetate on metabolic characteristics of LLC-PK1 cells. Basal respiration, maximal respiration, spare respiratory capacity and ATP-linked respiration were significantly increased in cells grown in growth medium supplemented with 5 mM acetoacetate. In contrast, glycolytic capacity, as well as glycolytic reserve were significantly reduced in the acetoacetate group. There was an increased expression in biomarkers of mitochondrial biogenesis, and an increase in mitochondrial protein expression. Cells grown in medium complemented with acetoacetate displayed...
Source: Toxicology Letters - January 18, 2020 Category: Toxicology Authors: Denoon T, Sunilkumar S, Ford SM Tags: Toxicol Lett Source Type: research

Mechanistic understanding of dendritic cell activation in skin sensitization: additional evidences to support potency classification.
MECHANISTIC UNDERSTANDING OF DENDRITIC CELL ACTIVATION IN SKIN SENSITIZATION: ADDITIONAL EVIDENCES TO SUPPORT POTENCY CLASSIFICATION. Toxicol Lett. 2020 Jan 17;: Authors: Galbiati V, Marinovich M, Corsini E Abstract Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to chemical allergens. In the EU, it has been calculated that 4% of animals are used in toxicity test for the assessment of skin sensitization [1]. To come a complete replacement of animals, evaluation of relative skin sensitization potency is necessary. The identification of...
Source: Toxicology Letters - January 17, 2020 Category: Toxicology Authors: Galbiati V, Marinovich M, Corsini E Tags: Toxicol Lett Source Type: research

Comparative Pharmacokinetics of Three Oximes in a Guinea Pig Model and Efficacy of Combined Oxime Therapy.
This study provides evidence that combination of oximes is effective and does not result in adverse events and that the pharmacokinetics of each oxime are not affected when administered in combination. PMID: 31954867 [PubMed - as supplied by publisher] (Source: Toxicology Letters)
Source: Toxicology Letters - January 16, 2020 Category: Toxicology Authors: Bohnert S, van den Berg RM, Mikler J, Klaassen SD, Joosen MJA Tags: Toxicol Lett Source Type: research

Repeated-oral dose toxicity of polyethylene microplastics and the possible implications on reproduction and development of the next generation.
Abstract With the increased distribution of microplastics in the environment, the potential for harmful effects on human health and ecosystems have become a global concern. Considering that polyethylene microplastics (PE-MPs) are among the most produced plastics worldwide, we administered PE-MPs (0.125, 0.5, 2 mg/day/mouse) by gavage to mice (10 mice/sex/dose) for 90 days. Compared to control, the body weight gain was significantly reduced in the male mice, and the proportion of neutrophils in the blood stream clearly increased in both sexes of mice. Persistence of a PE-MPs-like material and migration of gr...
Source: Toxicology Letters - January 16, 2020 Category: Toxicology Authors: Park EJ, Han JS, Park EJ, Seong E, Lee GH, Wan Kim D, Son HY, Han HY, Lee BS Tags: Toxicol Lett Source Type: research

Impact of soman and acetylcholine on the effects of propofol in cultured cortical networks.
Abstract Patients intoxicated with organophosphorous compounds may need general anaesthesia to enable mechanical ventilation or for control of epileptiform seizures. It is well known that cholinergic overstimulation attenuates the efficacy of general anaesthetics to reduce spontaneous network activity in the cortex. However, it is not clear how propofol, the most frequently used intravenous anaesthetic today, is affected. Here, we investigated the effects of cholinergic overstimulation induced by soman and acetylcholine on the ability of propofol to depress spontaneous action potential activity in organotypic cort...
Source: Toxicology Letters - January 16, 2020 Category: Toxicology Authors: Drexler B, Seeger T, Worek F, Thiermann H, Antkowiak B, Grasshoff C Tags: Toxicol Lett Source Type: research