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Toxicology Letters

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https://read.qxmd.com/read/30779948/the-relative-toxicity-of-brodifacoum-enantiomers
#1
Douglas L Feinstein, Kamil Gierzal, Asif Iqbal, Sergey Kalinin, Richard Ripper, Matthew Lindeblad, Alexander Zahkarov, Alexander Lyubimov, Richard van Breemen, Guy Weinberg, Israel Rubinstein
Brodifacoum (BDF) is a potent, long-acting anticoagulant rodenticide that can cause fatal poisoning in humans. The chemical structure of BDF includes 2 chiral carbons, resulting in 2 pairs of diastereomers, BDF-cis (R/S and S/R) and BDF-trans (R/R and S/S). However, the relative potency of these molecules is not known. The purpose of this study was to compare the in vitro and in vivo toxic effects of the 2 BDF diastereomer pairs. In adult Sprague-Dawley rats BDF-cis was significantly more toxic than BDF-trans (LD50 values of 219 versus 316 µg/kg, respectively) while racemic BDF had intermediate potency (266 µg/kg)...
February 16, 2019: Toxicology Letters
https://read.qxmd.com/read/30772500/stem-leydig-cell-regeneration-in-the-adult-rat-testis-is-inhibited-after-a-short-term-triphenyltin-exposure
#2
Chaobo Ni, Yinghui Fang, Xiuxiu Chen, Keyang Wu, Huitao Li, Yiyan Wang, Lin Zhenkun, Qingquan Lian, Ren-Shan Ge
Triphenyltin (TPT) is an organotin compound and may be an endocrine disruptor, impairing the male reproductive system. However, the effect of short-term TPT exposure on stem Leydig cell regeneration later on remains unknown. Here, we show that TPT affects stem Leydig cell regeneration in the adult rat testis. Adult male Sprague Dawley rats were gavaged with TPT (0, 0.5, 1.0, 2.0 mg/kg body weight/day) for 10 days, followed by a single intraperitoneal injection of ethane dimethane sulfonate (EDS, 75 mg/kg body weight) to eliminate Leydig cells...
February 14, 2019: Toxicology Letters
https://read.qxmd.com/read/30771440/aloe-emodin-induces-hepatotoxicity-by-activating-nf-%C3%AE%C2%BAb-inflammatory-pathway-and-p53-apoptosis-pathway-in-zebrafish
#3
Yunyun Quan, Lihong Gong, Junlin He, Yimeng Zhou, Meichen Liu, Zhixing Cao, Yunxia Li, Cheng Peng
The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate the hepatotoxicity mechanism of AE, the zebrafish Tg (fabp10: EGFP) was used as an animal model in vivo. The pathological sections of zebrafish liver were analyzed to observe the histopathological changes and Sudan black B was used to study whether there were inflammatory reactions in zebrafish liver or not...
February 13, 2019: Toxicology Letters
https://read.qxmd.com/read/30769083/kaempferol-reduces-k63-linked-polyubiquitination-to-inhibit-nuclear-factor-%C3%AE%C2%BAb-and-inflammatory-responses-in-acute-lung-injury-in-mice
#4
Jianchang Qian, Xuemei Chen, Xiaojun Chen, Chuchu Sun, Yuchen Jiang, Yuanyuan Qian, Yali Zhang, Zia Khan, Jianmin Zhou, Guang Liang, Chao Zheng
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), pose a major clinical challenge. The major driving force in this syndrome is pulmonary inflammation. Recent studies have shown that the naturally occurring flavonoid kaempferol (KPF) reduces endotoxin-induced inflammatory responses in mice. However, the mechanisms of these anti-inflammatory activities are not currently known. Here, we show that enhanced inflammatory cytokine production in response to lipopolysaccharide (LPS) is due to increased TGF-β-activated kinase-1 (TAK1) phosphorylation with subsequent activation of nuclear factor-κB (NF-κB)...
February 12, 2019: Toxicology Letters
https://read.qxmd.com/read/30769082/metabolism-of-nivalenol-and-nivalenol-3-glucoside-in-rats
#5
Heidi E Schwartz-Zimmermann, Sabina B Binder, Christian Hametner, Eugènia Miró-Abella, Christiane Schwarz, Herbert Michlmayr, Nicole Reiterer, Silvia Labudova, Gerhard Adam, Franz Berthiller
Plant-derived mycotoxin conjugates like deoxynivalenol-3-glucoside can be partly hydrolyzed to their aglycones in vivo, albeit to different extent depending on the mycotoxin conjugate and on the animal species. The aim of this work was to investigate the metabolization of the trichothecene mycotoxin nivalenol (NIV) and the fate of its modified form NIV-3-glucoside (NIV3 G) in rats. To that end, 350 µg/kg body weight of NIV and the equimolar dose of NIV3 G were administered to six rats by gavage in a 5 × 6 design and excreta were collected for 2 days after each treatment...
February 12, 2019: Toxicology Letters
https://read.qxmd.com/read/30769081/docosahexaenoic-acid-enhances-methylmercury-induced-endoplasmic-reticulum-stress-and-cell-death-and-eicosapentaenoic-acid-potentially-attenuates-these-effects-in-mouse-embryonic-fibroblasts
#6
Yasukazu Takanezawa, Ryosuke Nakamura, Miho Hamaguchi, Kanae Yamamoto, Yuka Sone, Shimpei Uraguchi, Masako Kiyono
Fish consumption has both the risk of methylmercury (MeHg) poisoning and the benefit of obtaining n-3 polyunsaturated fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). However, the cellular interaction between MeHg and PUFAs remains unknown. Therefore, the aim of this study was to investigate the effects of MeHg and n-3 PUFA exposure on mouse embryonic fibroblasts (MEFs). The results showed that EPA had a negligible effect on MeHg-induced cell death, whereas DHA promoted it...
February 12, 2019: Toxicology Letters
https://read.qxmd.com/read/30742882/chronic-lead-exposure-decreases-the-expression-of-huntingtin-associated-protein-1-hap1-through-repressor-element-1-silencing-transcription-rest
#7
Gaochun Zhu, Ting Peng, Chaohua Peng, He Li
Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence...
February 8, 2019: Toxicology Letters
https://read.qxmd.com/read/30742881/open-letter-to-the-german-research-foundation-dfg-deutsche-forschungsgemeinschaft-some-comments-on-the-recent-exclusion-of-a-renowned-scientist-from-a-toxicological-commission
#8
LETTER
https://read.qxmd.com/read/30742880/polychlorinated-biphenyl-quinone-induced-signaling-transition-from-autophagy-to-apoptosis-is-regulated-by-hmgb1-and-p53-in-human-hepatoma-hepg2-cells
#9
Qiong Shi, Yawen Wang, Wenjing Dong, Erqun Song, Yang Song
Autophagy, which works to remove stress and maintain cellular homeostasis, is usually considered a "pro-survival" signal. Contrarily, apoptosis is programmed "pro-death" machinery. Polychlorinated biphenyls (PCBs) are a group of ubiquitous industrial pollutants. Our previous studies illustrated that a PCB quinone metabolite, PCB29-pQ, elicited both autophagy and apoptosis. However, the signaling underlying the autophagy and apoptosis cross-talk has not been characterized. Here, we found that PCB29-pQ-induced autophagy mainly occurred at a lower concentration (5 μM), while apoptosis mostly arose at a higher concentration (15 μM) in HepG2 cells...
February 8, 2019: Toxicology Letters
https://read.qxmd.com/read/30735765/a-novel-investigation-of-statins-myotoxic-mechanism-effect-of-atorvastatin-on-respiratory-muscles-in-hypoxic-environment
#10
Samar O El-Ganainy, Ahmed El-Mallah, Dina Abdallah, Mahmoud M Khattab, Aiman S El-Khatib, Mahmoud M Mohy El-Din
Myopathy is a well-known adverse effect of statins, affecting a large sector of statins users. The reported experimental data emphasized on mechanistic study of statin myopathy on large muscles. Clinically, both large muscles and respiratory muscles are reported to be involved in the myotoxic profile of statins. However, the experimental data investigating the myopathic mechanism on respiratory muscles are still lacking. The present work aimed to study the effect of atorvastatin treatment on respiratory muscles using rat isolated hemidiaphragm in normoxic & hypoxic conditions...
February 5, 2019: Toxicology Letters
https://read.qxmd.com/read/30716388/an-in-vitro-model-to-evaluate-the-impact-of-environmental-fine-particles-pm-0-3-2-5-on-skin-damages
#11
Anthony Verdin, Fabrice Cazier, Richard Fitoussi, Natacha Blanchet, Katell Vié, Dominique Courcot, Isabelle Momas, Nathalie Seta, Sophie Achard
Exposure to airborne particulate matter (PM) has significant effects on human health mainly leading to cardio-respiratory diseases. However very few data are available regarding the impact of PM on the skin, so to better understand the impact of fine particle (PM0.3-2.5 ) on both inflammatory response and epidermal structure, we exposed a reconstructed human epidermis (RHE) to several doses of PM collected in Cotonou (Benin, West Africa). After 24 h of exposure, inflammatory response, histological observations, and gene expression related to oxidative stress, antioxidant defense and structural damages were determined...
February 1, 2019: Toxicology Letters
https://read.qxmd.com/read/30711673/neurotoxic-effects-of-perfluoroalkyl-acids%C3%AF-neurobehavioral-deficit-and-its-molecular-mechanism
#12
Yu Wang, Ling Wang, Wenguang Chang, Yinfeng Zhang, Yuan Zhang, Liu Wei
Perfluoroalkyl acids (PFAAs), as a group of industrial chemicals, are characterized by persistence, long-distance transmission, bioaccumulation and toxicity, and have been recognized as persistent organic pollutants. However, PFAAs and their related products have been used daily and in industrially products over the past several decades, which resulting in ubiquitous presence in various environmental medias, biota and even in human body. Numerous studies have investigated the neurobehavioral deficit and molecular mechanism underlying those effects of PFAAs in the last decades...
January 31, 2019: Toxicology Letters
https://read.qxmd.com/read/30711672/identification-of-pre-and-pro-haptens-with-a-%C3%AE-galactosidase-expressing-e-coli-culture-system-for-skin-sensitization
#13
Mahesh Raj Nepal, Mi Jeong Kang, Geon Ho Kim, Dong Ho Cha, Doo Hyun Nam, Tae Cheon Jeong
Although several in vitro approaches were successful in separating chemicals as skin sensitizers and non-sensitizers, none of the available methods completely mimics the absolute in vivo scenario of skin sensitization. One of the major challenges with currently available systems would be the limited or no metabolic capacity to activate pre- or pro-haptens to reactive metabolites in the system. In the present study, E. coli cells with β-galactosidase-expressing LacZ gene were combined with either induced rat liver S-9 fractions or microsomal fractions to detect pre- or pro-haptens to cause skin sensitization...
January 31, 2019: Toxicology Letters
https://read.qxmd.com/read/30711671/in-vitro-pulmonary-and-vascular-effects-induced-by-different-diesel-exhaust-particles
#14
Rossella Bengalli, Alessandra Zerboni, Sara Marchetti, Eleonora Longhin, Marco Priola, Marina Camatini, Paride Mantecca
Diesel exhaust particles (DEP) are responsible for both respiratory and cardiovascular effects. However many questions are still unravelled and the mechanisms behind the health effects induced by the exposure to ultrafine particles (UFP) need further investigations. Furthermore, different emission sources can lead to diverse biological responses. In this perspective, here we have compared the effects of three DEPs, two standard reference materials (SRM 1650b and 2975) and one DEP directly sampled from a EuroIV vehicle without Diesel Particulate Filter (DPF)...
January 31, 2019: Toxicology Letters
https://read.qxmd.com/read/30710622/apelin-13-reduces-oxidative-stress-induced-by-uric-acid-via-downregulation-of-renin-angiotensin-system-in-adipose-tissue
#15
Junxia Zhang, Xue Lin, Jinxiu Xu, Feng Tang
Apelin-13, a novel adipocytokine, is found to be a powerful antioxidant. Our previous work reported that uric acid could induce oxidative stress via an activation of renin-angiotensin system (RAS) in 3T3-L1 adipocytes. In the present study, we tried to observe the effect of apelin-13 on uric acid-induced oxidative stress. We also tried to reveal the potential mechanisms. In vivo, the rats were fed with 60% fructose diet for 8 weeks to produce hyperuricemia. Then, the hyperuricemia rats were intraperitoneally injected with apelin-13 for 2 weeks or 12 weeks...
January 30, 2019: Toxicology Letters
https://read.qxmd.com/read/30708112/hydrolyzed-fumonisin-b-1-induces-less-inflammatory-responses-than-fumonisin-b-1-in-the-co-culture-model-of-porcine-intestinal-epithelial-and-immune-cells
#16
Min Jeong Gu, Seung Eun Han, Kyoryen Hwang, Elisabeth Mayer, Nicole Reisinger, Dian Schatzmayr, Byung-Chul Park, Seung Hyun Han, Cheol-Heui Yun
Fumonisin B1 (FB1 ), mainly produced by Fusarium verticillioides and Fusarium proliferatum, can be converted to the less toxic metabolite hydrolyzed FB1 (HFB1 ) by enzymatic degradation. The application of an FB1 degrading enzyme as a feed additive is a strategy to reduce fumonisin exposure of animals. However, the difference between the effect of FB1 and HFB1 on porcine intestinal immunity is poorly documented. We investigated the toxic effects of FB1 and HFB1 exposure on porcine gut barrier function and intestinal immunity by using a co-culture model of intestinal porcine epithelial cells (IPEC-J2) and porcine peripheral blood mononuclear cells (PBMCs)...
January 29, 2019: Toxicology Letters
https://read.qxmd.com/read/30690063/review-of-transcriptomic-responses-to-hexavalent-chromium-exposure-in-lung-cells-supports-a-role-of-epigenetic-mediators-in-carcinogenesis
#17
Julia E Rager, Mina Suh, Grace A Chappell, Chad M Thompson, Deborah M Proctor
Inhalation exposure to hexavalent chromium [Cr(VI)] is associated with increased risk of lung cancer with a mode of action (MOA) postulated to involve non-mutagenic key events, yet molecular-level events remain uncertain. Previously-published transcriptomic studies in the lung and lung cells were reviewed to evaluate molecular events in the MOA. This study aimed to (i) identify biological pathways that are consistently modulated by Cr(VI) in the lung through the compilation of transcriptomic-based databases, (ii) predict interactions between epigenetic regulators and transcriptional responses, and (iii) relate findings to previous literature to postulate a mechanism of action underlying Cr(VI)-induced lung cancer involving changes in genomic/epigenomic signatures...
January 25, 2019: Toxicology Letters
https://read.qxmd.com/read/30690062/acute-exposure-to-deoxynivalenol-inhibits-porcine-enteroid-activity-via-suppression-of-the-wnt-%C3%AE-catenin-pathway
#18
Xiang-Guang Li, Min Zhu, Ming-Xia Chen, Hong-Bo Fan, Hou-Long Fu, Jia-Yi Zhou, Zhen-Ya Zhai, Chun-Qi Gao, Hui-Chao Yan, Xiu-Qi Wang
The intake of food containing deoxynivalenol frequently causes damage to the intestine, the renewal of which is driven by intestinal stem cells (ISCs). Nevertheless, the toxicity of deoxynivalenol on ISCs and its underlying mechanisms remain to be elucidated. As pigs are the most sensitive animals to deoxynivalenol, we used piglets for investigation in this study. Here, we show that intestinal epithelial cell activity, B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) protein level, and Wnt/β-catenin pathway activity were suppressed with acute expose to deoxynivalenol...
January 25, 2019: Toxicology Letters
https://read.qxmd.com/read/30684585/naphthalene-genotoxicity-dna-adducts-in-primate-and-mouse-airway-explants
#19
Sarah A Carratt, Matthew Hartog, Bruce A Buchholz, Edward A Kuhn, Nicole M Collette, Xinxin Ding, Laura S Van Winkle
Naphthalene (NA) is a ubiquitous environmental pollutant and possible human carcinogen that forms tumors in rodents with tissue/regional and species selectivity. This study seeks to determine whether NA is able to directly adduct DNA in an ex vivo culture system. Metabolically active lung tissue was isolated and incubated in explant culture with carbon-14 labeled NA (0, 25, 250μM) or 1,2-naphthoquinone (NQ), followed by AMS analyses of metabolite binding to DNA. Despite relatively low metabolic bioactivation in the primate airway, dose-dependent NA-DNA adduct formation was detected...
January 23, 2019: Toxicology Letters
https://read.qxmd.com/read/30682400/tools-for-studying-the-metabolism-of-new-psychoactive-substances-for-toxicological-screening-purposes-a-comparative-study-using-pooled-human-liver-s9-heparg-cells-and-zebrafish-larvae
#20
Lilian H J Richter, Jennifer Herrmann, Anastasia Andreas, Yu Mi Park, Lea Wagmann, Veit Flockerzi, Rolf Müller, Markus R Meyer
New psychoactive substances (NPS) are an emerging topic amongst abused compounds. New varieties appear constantly on the market, without any knowledge about their toxicodynamic and/or -kinetic properties and knowledge of their metabolism is crucial for the development of analytical methods employed for their detection. Controlled human studies would of course be best suited but due to ethical reasons and lack of preclinical safety data, they are usually not available. Often, in vitro models are used to evaluate similarities to human in vivo hepatic phase I and II metabolism and systems explored include primary human hepatocytes, pooled human S9 fraction, and HepaRG, a human hepatic cell line...
January 22, 2019: Toxicology Letters
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