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Toxicology Letters

Shahriar Khateri, Mahdi Balali-Mood, Peter Blain, Faith Williams, Paul Jowsey, Mohammad Reza Soroush, Effat Behravan, Mahmood Sadeghi
Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant...
December 4, 2017: Toxicology Letters
Georg Aichinger, Hannes Puntscher, Julia Beisl, Mary-Liis Kütt, Benedikt Warth, Doris Marko
Alternaria spp. are ubiquitous molds that are able to produce toxic secondary metabolites which may contaminate food globally. One of those is the mycotoxin altertoxin II (ATX-II), a genotoxic and mutagenic compound. In recent years, different flavonoids that may co-occur with mycotoxins in food were demonstrated to temper toxic effects of molds, mostly through their anti-oxidant properties. Thus, in this study, we assessed the influence of the berry anthocyanidin delphinidin on the toxicity of ATX-II in HT-29 colon carcinoma cells...
December 4, 2017: Toxicology Letters
Yujie Qiao, Lina Xu, Xufeng Tao, Lianhong Yin, Yan Qi, Youwei Xu, Xu Han, Zeyao Tang, Xiaodong Ma, Kexin Liu, Jinyong Peng
In the present work, the effects and possible mechanisms of dioscin, one natural product from the famous vegetable Dioscoreae rhizoma (Shanyao in Chinese), against high fructose-induced renal injury in rats were tested. The results showed that dioscin significantly restored fructose-induced renal injury by decreasing the levels of Cr, BUN, and rehabilitating histopathological changes. In addition, dioscin markedly adjusted the levels of MDA, SOD and GSH-Px, reduced ROS level in renal tissue, and decreased the levels of TG, FFA, α-SMA and COL1A...
December 2, 2017: Toxicology Letters
K Wright, S W Bihaqi, A Lahouel, A Masoud, F Mushtaq, A Leso, A Eid, N H Zawia
Previous reports by us have determined that developmental exposure to the heavy metal lead (Pb) resulted in cognitive impairment in aging wildtype mice, and a latent induction in biomarkers associated with both the tau and amyloid pathways. However, the relationship between these two pathways and their correlation to cognitive performance needs to be scrutinized. Here, we investigated the impact of developmental Pb (0.2%) exposure on the amyloid and tau pathways in a transgenic mouse model lacking the tau gene...
December 1, 2017: Toxicology Letters
L Escrivá, D Jennen, F Caiment, L Manyes
Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5μM; 24h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations...
December 1, 2017: Toxicology Letters
Katarzyna E Lazarska, Stefan J Dekker, Nico P E Vermeulen, Jan N M Commandeur
The use of diclofenac is associated with rare but severe drug-induced liver injury (DILI) in a very small number of patients. The factors which predispose susceptible patients to hepatotoxicity of diclofenac are still incompletely understood. Formation of protein-reactive metabolites by UDP-glucuronosyl transferases and cytochromes P450 is commonly considered to play an important role, as indicated by the detection of covalent protein adducts and antibodies in the serum of patients suffering from diclofenac-induced liver injury...
December 1, 2017: Toxicology Letters
Dorothee Rose, Annette Schmidt, Matthias Brandenburger, Tabea Sturmheit, Marietta Zille, Johannes Boltze
Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects...
December 1, 2017: Toxicology Letters
Kota Sekiguchi, Erina Ogawa, Kohta Kurohane, Hideyuki Konishi, Narumi Mochizuki, Kei Manabe, Yasuyuki Imai
Little attention has been paid to chemicals that can enhance hypersensitivity caused by other chemicals. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such an enhancing effect were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels, which are expressed on a part of sensory neurons, using a TRPA1-expressing cell line. In this study, we examined these activities of esters comprising glycerol and a short chain fatty acid, i...
November 30, 2017: Toxicology Letters
Kaviyarasi Renu, Harishkumar Madhyastha, Radha Madhyastha, Masugi Maruyama, Sankarganesh Arunachlam, Abilash V G
Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear...
November 30, 2017: Toxicology Letters
Michael Schwenk
Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation...
November 29, 2017: Toxicology Letters
María Laura Fernández, Pablo Yunes Quartino, Ruth Arce-Bejarano, Julián Fernández, Luis F Camacho, José María Gutiérrez, Daniel Kuemmel, Gerardo Fidelio, Bruno Lomonte
A unique feature of the venom of Micrurus fulvius (Eastern coral snake) is its ability to induce severe intravascular hemolysis in particular species, such as dogs or mice. This effect was previously shown to be induced by distinct phospholipase A2 (PLA2) isoforms which cause direct hemolysis in vitro, an uncommon finding for such enzymes. The functional profiles of PLA2-17, a direct hemolytic enzyme, and PLA2-12, a co-existing venom isoform lacking such effect, were compared. The enzymes differed not only in their ability to cause intravascular hemolysis: PLA2-17 additionally displayed lethal, myotoxic, and anticoagulant actions, whereas PLA2-12 lacked these effects...
November 29, 2017: Toxicology Letters
Mohammad Mehdi Ommati, Reza Heidari, Akram Jamshidzadeh, Mohammad Javad Zamiri, Zilong Sun, Samira Sabouri, Jundong Wang, Fatemeh Ahmadi, Nafiseh Javanmard, Kazem Seifi, Saeed Mousapour, Babak Shirazi Yeganeh
There are reports of sulfasalazine (Salazosulfapyridine; SASP)-induced reproductive toxicity, but there it is not known whether the SASP molecule or its intestinal metabolites are responsible for this effect. Rats received SASP (150, 300, and 600mg/kg) for 60 consecutive days (in vivo). Additionally, epididymal sperm was isolated and incubated with SASP (10μM-1600μM) (in vitro). Markers of oxidative stress, mitochondrial function, and sperm functionality, along with testis histopathology as well as several steroidogenic genes and proteins, including steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage enzyme (P450scc; Cyp11a), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) were measured...
November 29, 2017: Toxicology Letters
Han Zhang, Jing Chen, Ziyan Shen, Yulu Gu, Linghan Xu, Jiachang Hu, Xiaoyan Zhang, Xiaoqiang Ding
Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification...
November 28, 2017: Toxicology Letters
Hong Chen, Qun Chen, Chun-Ming Jiang, Guang-Yue Shi, Bo-Wen Sui, Wei Zhang, Li-Zhen Yang, Zhu-Ying Li, Li Liu, Yu-Ming Su, Wen-Cheng Zhao, Hong-Qiang Sun, Zhen-Zi Li, Zhou Fu
Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFβ plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells...
November 28, 2017: Toxicology Letters
Corinna Scheffel, Karin V Niessen, Sebastian Rappenglück, Klaus T Wanner, Horst Thiermann, Franz Worek, Thomas Seeger
Organophosphorus compounds, including nerve agents and pesticides, exert their toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting in an accumulation of acetylcholine and functional impairment of muscarinic and nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate AChE and atropine to antagonize effects induced by muscarinic acetylcholine receptors. Nicotinic malfunction leading to depression of the central and peripheral respiratory system is not directly treated calling for alternative therapeutic interventions...
November 27, 2017: Toxicology Letters
Jessica Scheider, Fabian Afonso-Grunz, Luzie Jessl, Klaus Hoffmeier, Peter Winter, Jörg Oehlmann
Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially expressed genes that are linked to morphological alterations of gonadal tissue from chicken embryos after exposure to TBT. We applied a single injection of TBT (between 0.5 and 30pg as Sn/g egg) into incubated fertile eggs to simulate maternal transfer of the endocrine disruptive compound...
November 27, 2017: Toxicology Letters
Annette Schmidt, Dirk Steinritz, Klaus-Dieter Rudolf, Horst Thiermann, Enno Striepling
The clinical progression following a sulfur mustard-induced skin exposure is well documented in the literature. Upon skin contact and a characteristic latency period, sulfur mustard (SM) causes erythema, blister formation and ulceration, which is associated with wound healing disorders that may require surgical treatment. Here, we present a case report of accidental exposure to SM in a laboratory setting which required surgical treatment of the skin. The case was illustrated at close intervals over a period of two years and underlines that exposure to SM has to be taken into account when typical clinical symptoms occur...
November 27, 2017: Toxicology Letters
T M Mann, M E Price, C L Whitmore, R L Perrott, T R Laws, R R McColm, E R Emery, J E H Tattersall, A C Green, H Rice
The prolonged systemic exposure that follows skin contamination with low volatility nerve agents, such as VX, requires treatment to be given over a long time due to the relatively short half-lives of the therapeutic compounds used. Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide effective post-exposure protection against percutaneous nerve agent when given immediately on signs of poisoning and to reduce reliance on additional treatments. In order to assess the benefits of administration of bioscavenger at later times, its effectiveness was assessed when administration was delayed for 2h after the appearance of signs of poisoning in guinea-pigs challenged with VX (4×LD50)...
November 25, 2017: Toxicology Letters
Simone Rothmiller, Sarah Schröder, Romano Strobelt, Markus Wolf, Jin Wang, Xiqian Jiang, Franz Worek, Dirk Steinritz, Horst Thiermann, Annette Schmidt
BACKGROUND: Sulfur mustard (SM) is a potent blistering chemical warfare agent, which was first used in 1917. Despite the Chemical Weapons Convention, a use was recently reported in Syria in 2015. This emphasizes the importance to develop countermeasures against chemical warfare agents. Despite intensive research, there is still no antidote or prophylaxis available against SM. METHODS: The newly developed SM-resistant keratinocyte cell line HaCaT/SM was used to identify new target structures for drug development, particularly the adaptations in protective measures against oxidative stress...
November 25, 2017: Toxicology Letters
Monique Chalansonnet, Nathalie Carabin, Stéphane Boucard, Lise Merlen, Mathieu Melczer, Guillaume Antoine, Jérôme Devoy, Aurélie Remy, François Gagnaire
Many employees in the aluminum industry are exposed to a range of aluminum compounds by inhalation, and the presence of ultrafine particles in the workplace has become a concern to occupational health professionals. Some metal salts and metal oxides have been shown to enter the brain through the olfactory route, bypassing the blood-brain barrier, but few studies have examined whether aluminum compounds also use this pathway. In this context, we sought to determine whether aluminum was found in rat olfactory bulbs and whether its transfer depended on physicochemical characteristics such as solubility and granulometry...
November 24, 2017: Toxicology Letters
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