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Toxicology Letters

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https://www.readbyqxmd.com/read/30012503/plasma-citrulline-is-a-sensitive-safety-biomarker-for-small-intestinal-injury-in-rats
#1
Wataru Saitoh, Sanae Takada, Jun Hirao, Makoto Shirai, Takuma Iguchi, Makoto Tsuji, Takayoshi Nishiya, Kazuhiko Mori
Plasma citrulline is decreased in cases of severe intestinal injury with apparent villus and cellular atrophy. However, the fluctuation of plasma citrulline in slight intestinal injury remains to be investigated. To clarify this, irinotecan at 30 mg/kg or 60 mg/kg was administered intravenously to rats. Irinotecan reduced plasma citrulline concentrations compared to those in the pair-fed control, being concurrent with slight single cell necrosis and mucosal epithelium regeneration in the small intestine without apparent villus and cellular atrophy...
July 13, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30010034/transplacental-transfer-and-metabolism-of-diuron-in-human-placenta
#2
Ali Mustafa Mohammed, Vesa Karttunen, Pasi Huuskonen, Marjo Huovinen, Seppo Auriola, Kirsi Vähäkangas
Diuron is a broad-spectrum phenylurea derived herbicide which is commonly used across the globe. Diuron is toxic to the reproductive system of animals and carcinogenic to rat urothelium, and recently found to be genotoxic in human cells. In in vivo, it is metabolized predominately into 3-(3,4-dichlorophenyl)-1-methyl urea (DCPMU) in humans and 3-(3, 4-dichlorophenyl)urea (DCPU) in animals. Information on diuron toxicokinetics and related toxicity in human placenta is absent. We have investigated the toxicokinetics of diuron in ex vivo human placental perfusion and in in vitro human placental microsomes and human trophoblastic cancer cells (BeWo)...
July 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30010033/dnmt1-controls-lncrna-h19-erk-signal-pathway-in-hepatic-stellate-cell-activation-and-fibrosis
#3
Jing-Jing Yang, Qian She, Yan Yang, Hui Tao, Jun Li
Hepatic stellate cells (HSCs) activation is considered as a pivotal event in liver fibrosis. In HSCs activation and fibrosis, epigenetic events are important. Although HSCs activation alters DNA methylation, it is unknown, whether it also affects other epigenetic processes, including LncRNA and its recognition. The aim of this study was to identify the mechanism of DNA methyltransferase 1 (DNMT1) expression and its role in regulating LncRNA H19 during HSCs activation and fibrosis. Expression of DNMT1 and LncRNA H19 were determined in activated HSCs and CCl4 -induced rat liver fibrosis tissue...
July 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30006252/endocrine-disruption-current-approaches-for-regulatory-testing-and-assessment-of-plant-protection-products-are-fit-for-purpose
#4
Peter Day, Richard M Green, Melanie Gross, Lennart Weltje, James R Wheeler
The ongoing debate concerning the regulation of endocrine disruptors, has increasingly led to questions concerning the current testing of chemicals and whether this is adequate for the assessment of potential endocrine disrupting effects. This paper describes the current testing approaches for plant protection product (PPP) active substances in the European Union and the United States and how they relate to the assessment of endocrine disrupting properties for human and environmental health. This includes a discussion of whether the current testing approaches cover modalities other than the estrogen, androgen, thyroid and steroidogenesis (EATS) pathways, sensitive windows of exposure, adequate assessment of human endocrine disorders and wildlife species, and the determination of thresholds for endocrine disruption...
July 10, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30003948/urinary-levels-of-metal-elements-in-the-non-smoking-general-population-in-italy-sivr-study-2012-2015
#5
Maria Cristina Aprea, Pietro Apostoli, Maurizio Bettinelli, Piero Lovreglio, Sara Negri, Luigi Perbellini, Andrea Perico, Maria Cristina Ricossa, Fabiola Salamon, Maria Luisa Scapellato, Ivo Iavicoli
The purpose of this study of the Italian Society of Reference Values (SIVR) was to provide the reference values for metals in the urine of the Italian general population. Thirteen sampling centres situated in the north, centre and south of Italy took part in this project. Each sampling centre selected 20 adult subjects. The sample was made up of 120 male and 140 female non-smokers or smokers who had abandoned the habit at least 5 years previously, aged between 18 and 60 years. Urine samples were obtained from the same subjects in June and again in November of the same year...
July 9, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30008432/ammonia-role-in-glial-dysfunction-in-methylmalonic-acidemia
#6
Patricia Gabbi, Viviane Nogueira, Fernanda Haupental, Fernanda Silva Rodrigues, Patricia Severo do Nascimento, Sílvia Barbosa, Josi Arend, Ana Flávia Furian, Mauro Schneider Oliveira, Adair Roberto Soares Dos Santos, Luiz Fernando Freire Royes, Michele Rechia Fighera
Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution to methylmalonate (MMA)-induced neurotoxicity is poorly understood. The aim of this study was evaluate whether an acute metabolic damage to brain during the neonatal period may disrupt cerebral development, leading to neurodevelopmental disorders, as memory deficit. Mice received a single intracerebroventricular dose of MMA and/or NH4 Cl, administered 12 hs after birth. The maze tests showed that MMA and NH4 Cl injected animals (21 and 40 days old) exhibited deficit in the working memory test, but not in the reference memory test...
July 7, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29990563/suitability-of-several-naphthalene-metabolites-for-their-application-in-biomonitoring-studies
#7
Katrin Klotz, Melanie Zobel, Anja Schäferhenrich, Ralph Hebisch, Hans Drexler, Thomas Göen
Naphthalene occurs together with polycyclic aromatic hydrocarbons (PAHs) at industrial workplaces and is ubiquitous in the environment. For biological monitoring of naphthalene exposures, up to now mainly 1- and 2-naphthol in urine have been used. Recently, we proposed 1,2-dihydroxynaphthalene (1,2-DHN) and the 1- and 2-naphthylmercapturic acid (1- and 2-NMA) as new urinary biomarkers to characterise a naphthalene exposure. In this study, in a collective of nine occupationally exposed workers handling with creosote the naphthalene metabolites 1,2-DHN, 1- and 2-NMA as well as 1- and 2-naphthol were analysed in order to evaluate the suitability of the different parameters for their application in biomonitoring studies...
July 7, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29990562/chronic-iron-overload-induces-vascular-dysfunction-in-resistance-pulmonary-arteries-associated-with-right-ventricular-remodeling-in-rats
#8
Sabrina Rodrigues Bertoli, Vinicius Bermond Marques, Emilly Martinelli Rossi, Maiara Krause, Maria Tereza Weitzel Dias Carneiro Lima, Maylla Ronacher Simões, Leonardo Dos Santos
Although iron excess is toxic to the cardiovascular system and even that pulmonary hypertension has been reported, the role of iron overload per se remains to be clarified. This study aimed to test the effects of chronic iron-overload in rats on the morphophysiology of resistance pulmonary arteries (RPA) and right ventricle (RV) remodeling. Rats were injected with saline or iron-dextran (10, 100 and 200 mg/kg/day i.p.) for 28 days. Our results indicated increased circulating iron with significant lung deposits...
July 7, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29990561/response-of-intestinal-ht-29-cells-to-the-trichothecene-mycotoxin-deoxynivalenol-and-its-sulfated-conjugates
#9
Giorgia Del Favero, Lydia Woelflingseder, Dominik Braun, Hannes Puntscher, Mary-Liis Kütt, Luca Dellafiora, Benedikt Warth, Gudrun Pahlke, Chiara Dall'Asta, Gerhard Adam, Doris Marko
The sulfated forms of the Fusarium toxin deoxynivalenol (DON), deoxynivalenol-3-sulfate (DON-3-Sulf) and deoxynivalenol-15-sulfate (DON-15-Sulf) were recently described, however little is known about their mechanism of action in mammalian cells. DON-3-Sulf and DON-15-Sulf were taken up by HT-29 colon carcinoma cells, although to a lesser extent compared to DON. All three compounds were found to enhance the intracellular ROS level in the dichlorofluorescein assay (≥ 1µM), even though substantial differences were observed in their cytotoxic potential...
July 7, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29981923/in-silico-approach-for-drug-induced-liver-injury-prediction-recent-advances
#10
Neha Saini, Shikha Bakshi, Sadhna Sharma
Drug induced liver injury (DILI) is the prime cause of liver disfunction which may lead to mild non-specific symptoms to more severe signs like hepatitis, cholestasis, cirrhosis and jaundice. Not only the prescription medications, but the consumption of herbs and health supplements have also been reported to cause these adverse reactions resulting into high mortality rates and post marketing withdrawal of drugs. Due to the continuously increasing DILI incidences in recent years, robust prediction methods with high accuracy, specificity and sensitivity are of priority...
July 5, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29981922/poly-adp-ribose-glycohydrolase-silencing-mediated-maintenance-of-h2a-and-downregulation-of-h2ak9me-protect-human-bronchial-epithelial-cells-from-benzo-a-pyrene-induced-carcinogenesis
#11
Zhuoying Zeng, Hailong Liu, Jianhui Yuan, Xiaohu Ren, Yanxia Deng, Wenjuan Dai, Yue Wu, Yun Huang, Ruixue Huang, Jiaofeng Liu, Haiyan Huang, Jian'an Hu
Poly (ADP-ribosylation) is a key post-translational modification (PTM), and poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme that hydrolyzes poly (ADP-ribose) in eukaryotic organisms. Our previous findings suggested that knockdown of PARG attenuates benzo(a)pyrene (BaP) carcinogenesis. However, the mechanisms underlying PARG-mediated protective effects remain limited. In this study, the expression levels of histones were analyzed by Western blotting and immunofluorescence. Histone H2A levels were abnormally decreased by BaP-induced carcinogenesis, but were maintained by knockdown of PARG in the 16HBE human bronchial epithelial cell line...
July 5, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29981921/prenatal-nicotine-exposure-retards-osteoclastogenesis-and-endochondral-ossification-in-fetal-long-bones-in-rats
#12
Hang Hu, Xin Zhao, Jing Ma, Yangfan Shangguan, Zhengqi Pan, Liaobin Chen, Xianrong Zhang, Hui Wang
This study investigated the mechanisms underlying the retarded development of long bone in fetus by prenatal nicotine exposure (PNE) which had been demonstrated by our previous work. Nicotine (2.0 mg/kg.d) or saline was injected subcutaneously into pregnant rats every morning from gestational day (GD) 9 to 20. Fetal femurs or tibias were harvested for analysis on GD 20. We found massive accumulation of hypertrophic chondrocytes and a delayed formation of primary ossification center (POC) in the fetal femur or tibia of rat fetus after PNE, which was accompanied by a decreased amount of osteoclasts in the POC and up-regulated expression of osteoprotegerin (OPG) but by no obvious change in the expression of receptor activator of NF-κB ligand (RANKL)...
July 5, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29981920/fluorochloridone-perturbs-blood-testis-barrier-sertoli-cell-barrier-function-through-arp3-mediated-f-actin-disruption
#13
Luqing Liu, Yubin Zhang, Xiuli Chang, Rui Li, Chunhua Wu, Liming Tang, Zhijun Zhou
There are reports of fluorochloridone (FLC)-induced male reproductive toxicity, but the underlying toxicological mechanisms remain unknown. In this study, we looked at how FLC exposure affected the integrity of the blood-testis barrier (BTB) and the Sertoli cell barrier and studied the molecular mechanisms. Male rats received gavage administration of FLC (30 mg/kg/d) for 14 consecutive days with sample collection at the 7th and 14th day; and primary cultured Sertoli cells were treated with 0-10 μM FLC in vitro for 24 h...
July 5, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29981919/the-cardenolides-strophanthidin-digoxigenin-and-dihydroouabain-act-as-activators-of-the-human-ror%C3%AE-ror%C3%AE-t-receptors
#14
Kaja Karaś, Anna Sałkowska, Aurelia Walczak-Drzewiecka, Katarzyna Ryba, Jarosław Dastych, Rafał A Bachorz, Marcin Ratajewski
Two isoforms of a ligand-activated nuclear receptor, RORγ and RORγT, have been implicated in various physiological functions, including energy metabolism, circadian rhythm and immune system development. Using a stably transfected reporter cell line, we screened two chemical libraries and identified three cardenolides (natural, plant-derived pesticides) as activators of RORγ-dependent transcription. These compounds increased G6PC and NPAS2 expression in HepG2 cells, accompanied by increased occupancy of RORγ within the promoters of these genes...
July 5, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29966748/prenatal-caffeine-exprosure-increases-adult-female-offspring-rat-s-susceptibility-to-osteoarthritis-via-low-functional-programming-of-cartilage-igf-1-with-histone-acetylation
#15
Yang Tan, Kaihang Lu, Jing Li, Qubo Ni, Zhe Zhao, Jacques Magdalou, Liaobin Chen, Hui Wang
Our previous in vivo studies showed that prenatal caffeine exposure (PCE) could restrain the development of chondrogenesis, which may delay fetal articular cartilage development and increase susceptibility to osteoarthritis in adults. So, the goal of the current study is to clarify theincreasing susceptibility to adult osteoarthritis in caffeine-exposed female offspring and its'mechanism. Pregnant rats were treated with 120 mg/kg·d caffeine or equal volumes of saline from gestational day (GD) 9 to 20. knee joints were collected from GD20 female fetuses and 18-week old female offspring which was treated with strenuous running for 6 weeks (55 min/day at 20 m/min) load to induce osteoarthritis...
June 29, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29966747/re-defining-kinetic-lung-overload-time-for-new-paradigms
#16
Wenli Li, Juergen Pauluhn
This paper compares two previously published 13-week inhalation studies with poorly soluble, low-toxicity particles (PSLTs) in rats to identify the unifying key metric of kinetic lung overload. The PSLTs compared are Multi-Walled Carbon Nanotubes (MWCNT) and black iron oxide (Fe3 O4 , magnetite). Their material densities and related displacement volumes differ approximately 30-fold. This offers an opportunity for analyzing the impact of the PSLT-density of agglomerates on endpoints currently conceived to be involved in kinetic lung overload...
June 29, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29964132/jbp485-attenuates-vancomycin-induced-nephrotoxicity-by-regulating-the-expressions-of-organic-anion-transporter-oat-1-oat3-organic-cation-transporter-2-oct2-multidrug-resistance-associated-protein-2-mrp2-and-p-glycoprotein-p-gp-in-rats
#17
Shijie Wen, Changyuan Wang, Xiaokui Huo, Qiang Meng, Zhihao Liu, Shilei Yang, Yanna Zhu, Huijun Sun, Xiaodong Ma, Kexin Liu
The present study aimed to investigate the regulation of JBP485 on the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp), which can accelerate the renal excretion of accumulated endogenous toxins to attenuate vancomycin-induced nephrotoxicity (VIN) in rats. Vancomycin suppressed the mRNA and protein expressions of Oat1, Oat3, Oct2, Mrp2 and P-gp to reduce the renal excretion of endogenous toxins (e...
June 28, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29959987/tlr2-and-tlr3-expression-as-a-biomarker-for-the-risk-of-doxorubicin-induced-heart-failure
#18
Shao Liang, Cai Xinyong, Zhu Hongmin, Wang Jing, Hong Lang, Zhang Ping
Doxorubicin (Dox) is limited in its use because of its adverse effect of inducing irreversible heart dysfunction. Innate immune factors, including toll-like receptors (TLRs), play important roles in most cardiac diseases and doxorubicin-induced cardiotoxicity. In this study, subjects were divided into the following groups: healthy controls (n = 62), HF group (n = 60), Dox group (n = 82), and Dox-HF group (n = 32). Expressions of TLR mRNAs in peripheral blood mononuclear cells were detected by RT-PCR...
June 27, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29959986/inhibition-of-nrf2-alters-cell-stress-induced-by-chronic-iron-exposure-in-human-proximal-tubular-epithelial-cells
#19
S E G van Raaij, R Masereeuw, D W Swinkels, R P L van Swelm
Iron can catalyze reactive oxygen species (ROS) formation, causing cellular injury. In systemic iron overload, renal tubular epithelial cells are luminally exposed to high iron levels due to glomerular filtration of increased circulating iron. Reports of tubular dysfunction and iron deposition in β-thalassemia major support an association between increased chronic iron exposure and renal tubular injury. In acute iron exposure, Nuclear factor-erythroid 2-related factor 2 (Nrf2) may protect from iron-induced injury, whereas chronic renal stress may lead to Nrf2 exhaustion...
June 27, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29958929/development-of-a-human-physiologically-based-pharmacokinetic-pbpk-model-for-phthalate-dehp-and-its-metabolites-a-bottom-up-modeling-approach
#20
Raju Prasad Sharma, Marta Schuhmacher, Vikas Kumar
DEHP exposure to human comes from different sources such as food, diet, cosmetics, toys, medical products, and food wraps. Recently DEHP was categorized under non-persistent endocrine disruptor compounds (EDCs) by the world health organization (WHO). There is enough evidence from the rat experimental studies that phthalate causes hepatic, developmental and reproductive toxicity. In human, DEHP rapidly metabolizes into a toxic metabolite MEHP. This MEHP further metabolizes into the different chemical forms of 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP and phthalic acid...
June 26, 2018: Toxicology Letters
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