Yunbing Tang, Shi Lei, Shaowei Wang, Han Lu, Huitao Li, Jieqiang Lv, Ren-Shan Ge, Yingfen Ying
Perfluorotetradecanoic acid (PFTeDA) is a type of perfluoroalkyl acid that has been linked to various health effects in animals and humans. The study aimed to investigate the potential impact of PFTeDA exposure on Leydig cell development in rats during puberty. Understanding the effects of PFTeDA on Leydig cells is crucial as these cells play a significant role in male reproductive function. Male Sprague-Dawley rats were gavaged with PFTeDA at doses of 0, 1, 5, and 10mg/kg/day from postnatal day 35 to 56. The serum hormone levels were measured and testicular transcriptome changes were analyzed by RNA-seq and verified by qPCR, and the levels of steroidogenesis-related proteins and energy regulators were measured...
June 1, 2023: Toxicology Letters
Niko Amend, Horst Thiermann, Franz Worek, Timo Wille
Isolated organ models are a versatile tool for pharmacological and toxicological research. Small bowel has been used to assess the inhibition of smooth muscle contraction by opioids. In the present study, we set out to establish a pharmacologically stimulated rat bowel model. The effects of carfentanil, remifentanil and the new synthetic opioid U-48800 and their respective antagonists naloxone, nalmefene and naltrexone were studied in a small bowel model in rats. The IC50 values of the tested opioids were as follows: carfentanil (IC50 = 0...
May 26, 2023: Toxicology Letters
Yedan Lu, Pinpin Sui, Jinzhe Li, Nan Lian, Jin Zhou, Xiurong Cheng, Qian-Fei Wang, Caihong Xing, Peiyu Xu
Benzene is a known hematotoxic and leukemogenic chemical. Exposure to benzene cause inhibition of hematopoietic cells. However, the mechanism of how the hematopoietic cells inhibited by benzene undergo malignant proliferation is unknown. The cells carrying leukemia-associated fusion genes are present in healthy individuals and predispose the carriers to the development of leukemia. To identify the effects of benzene on hematopoietic cells, preleukemic bone marrow (PBM) cells derived from transgenic mice carrying the Mll-Af9 fusion gene were treated with benzene metabolite hydroquinone in serial replating of colony-forming unit (CFU) assay...
May 26, 2023: Toxicology Letters
Kristal A Rychlik, Emily J Illingworth, Ian F Sanchez, Sarah E Attreed, Prithvi Sinha, Kevin M Casin, Nicole Taube, Jeff Loube, Rokeya Tasneen, Raihan Kabir, Eric Nuermberger, Wayne Mitzner, Mark J Kohr, Fenna C M Sillé
Prenatal arsenic exposure is a major public health concern, associated with altered birth outcomes and increased respiratory disease risk. However, characterization of the long-term effects of mid-pregnancy (second trimester) arsenic exposure on multiple organ systems is scant. This study aimed to characterize the long-term impact of mid-pregnancy inorganic arsenic exposure on the lung, heart, and immune system, including infectious disease response using the C57BL/6 mouse model. Mice were exposed from gestational day 9 till birth to either 0 or 1000µg/L sodium (meta)arsenite in drinking water...
May 25, 2023: Toxicology Letters
Paulo Francisco Veiga Bizerra, Fernanda Sayuri Itou da Silva, Eduardo Hideo Gilglioni, Letícia Fernanda Nanami, Eduardo Makiyama Klosowski, Byanca Thais Lima de Souza, Ana Flávia Gatto Raimundo, Karina Borba Paulino Dos Santos, Juliana Moraes Mewes, Renato Polimeni Constantin, Márcio Shigueaki Mito, Emy Luiza Ishii-Iwamoto, Jorgete Constantin, Fábio Ermínio Mingatto, Giovana Natiele Machado Esquissato, Rogério Marchiosi, Wanderley Dantas Dos Santos, Osvaldo Ferrarese-Filho, Rodrigo Polimeni Constantin
Clomipramine, a tricyclic antidepressant used to treat depression and obsessive-compulsive disorder, has been linked to a few cases of acute hepatotoxicity. It is also recognized as a compound that hinders the functioning of mitochondria. Hence, the effects of clomipramine on mitochondria should endanger processes that are somewhat connected to energy metabolism in the liver. For this reason, the primary aim of this study was to examine how the effects of clomipramine on mitochondrial functions manifest in the intact liver...
May 20, 2023: Toxicology Letters
Hao Lin, Shaowei Wang, Yunbing Tang, Zhiyan Hu, Xiaofang Chen, Huitao Li, Yang Zhu, Yiyan Wang, Yi Liu, Ren-Shan Ge
Benzophenones (BPs) are a class of chemicals found in various personal care and cosmetic products, such as sunscreens and lotions. Their usage is known to cause reproductive and hormonal health risks, but the exact mechanism of action remains unknown. In this study, we investigated the effect of BPs on human and rat placental 3β-hydroxysteroid dehydrogenases (3β-HSDs), which play a crucial role in the biosynthesis of steroid hormones, particularly progesterone. We tested inhibitory effects of 12 BPs, and performed structure-activity relationship (SAR) and in silico docking analysis...
May 20, 2023: Toxicology Letters
S G Rudyak, L A Usakin, E A Tverye, E D Robertson, A A Panteleyev
Aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor activated by polycyclic aromatic hydrocarbons of synthetic and natural origin. While a number of novel AhR ligands have been recently identified, little is known about their possible influence on AhR levels and stability. We used western blot, qRT-PCR and immunocytochemistry to determine the effects of AhR ligands on AhR expression in N-TERT (N-TERT1) immortalized human keratinocytes, and immunohistochemistry to assess patterns of AhR expression in human and mouse skin and skin appendages...
May 20, 2023: Toxicology Letters
François Busquet, Jeanne Laperrouze, Katica Jankovic, Tamara Krsmanovic, Tomasz Ignasiak, Benedetta Leoni, Gordana Apic, Giovanni Asole, Roderic Guigó, Paolo Marangio, Emilio Palumbo, Silvia Perez-Lluch, Valentin Wucher, Anna Hendrika Vlot, Robert Anholt, Trudy Mackay, Beate I Escher, Nico Grasse, Julia Huchthausen, Riccardo Massei, Thorsten Reemtsma, Stefan Scholz, Gerrit Schüürmann, Maria Bondesson, Peter Cherbas, Jonathan H Freedman, Stephen Glaholt, Jessica Holsopple, Stephen C Jacobson, Thomas Kaufman, Ellen Popodi, Joseph J Shaw, Shannon Smoot, Jason M Tennessen, Gary Churchill, Christina Cramer von Clausbruch, Thomas Dickmeis, Gaëlle Hayot, Giuseppina Pace, Ravindra Peravali, Carsten Weiss, Nadezda Cistjakova, Xin Liu, Andis Slaitas, James Ben Brown, Rafael Ayerbe, Joan Cabellos, Elena Cerro-Gálvez, María Diez-Ortiz, Verónica González, Rubén Martínez, Patricia Solórzano Vives, Rosemary Barnett, Thomas Lawson, Robert G Lee, Elena Sostare, Mark Viant, Roland Grafström, Vesa Hongisto, Pekka Kohonen, Konrad Patyra, Pradeep Kumar Bhaskar, Marcial Garmendia-Cedillos, Ibraheem Farooq, Brian Oliver, Tom Pohida, Ghadi Salem, Daniel Jacobson, Elisabeth Andrews, Marianne Barnard, Aleksandra Čavoški, Anurag Chaturvedi, John K Colbourne, David J T Epps, Laura Holden, Martin R Jones, Xiaojing Li, Ferenc Müller, Agata Ormanin-Lewandowska, Luisa Orsini, Ruth Roberts, Ralf J M Weber, Jiarui Zhou, Mu-En Chung, Juan Carlos Gonzalez Sanchez, Gaurav D Diwan, Gurdeep Singh, Uwe Strähle, Robert B Russell, Dominique Batista, Susanna-Assunta Sansone, Philippe Rocca-Serra, David Du Pasquier, Gregory Lemkine, Barbara Robin-Duchesne, Andrew Tindall
The goal of PrecisionTox is to overcome conceptual barriers to replacing traditional mammalian chemical safety testing by accelerating the discovery of evolutionarily conserved toxicity pathways that are shared by descent among humans and more distantly related animals. An international consortium is systematically testing the toxicological effects of a diverse set of chemicals on a suite of five model species comprising fruit flies, nematodes, water fleas, and embryos of clawed frogs and zebrafish along with human cell lines...
May 19, 2023: Toxicology Letters
Devin I Alewel, Thomas W Jackson, Samuel A Vance, Mette C Schladweiler, Paul A Evansky, Andres R Henriquez, Rachel Grindstaff, Stephen H Gavett, Urmila P Kodavanti
Acrolein and trichloroethylene (TCE) are priority hazardous air pollutants due to environmental prevalence and adverse health effects; however, neuroendocrine stress-related systemic effects are not characterized. Comparing acrolein, an airway irritant, and TCE with low irritancy, we hypothesized that airway injury would be linked to neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30min, followed by 3...
May 16, 2023: Toxicology Letters
Ying Bai, Fang-Fang Li, Yi Zhang, Yu-Bin Ding
The wide application of silicon dioxide nanoparticles (SiO2 NPs) has raised concerns about their harmful effects on reproduction. The purpose of this research was to investigate the toxic effects and the possible mechanisms by which SiO2 NPs affect decidualization and pregnancy progression. We found that SiO2 NPs could inhibit decidualization, both in mice and in human endometrial stromal cells (HESCs). Embryo resorption was also evident in mice treated with SiO2 NPs. When HESCs were treated with SiO2 NPs, decidualization was inhibited and there was an increase in intracellular lysosomes and autophagosomes as well as the blockage of autophagic flux...
May 9, 2023: Toxicology Letters
A Kende, F Lai, P P Lim, L Swindale, A Hofstra, F Zhang, E McInnes, R Currie, D Cowie
In long term rodent studies administering Cyclobutrifluram (TYMIRIUM® Technology), a new agrochemical, there was a slight elevation of incidence of hepatocellular carcinomas in male CD-1 mice that was within the historical control range but appeared to be dose responsive. Cyclobutrifluram's ability to activate mouse constitutive androstane receptor (CAR) mediated gene transcription was confirmed in vitro, therefore a 28-day dietary toxicity study was conducted in vivo in male CD-1 mice to assess the CAR activation mode of action hypothesis of Cyclobutrifluram along with phenobarbital, a known CAR activator...
May 8, 2023: Toxicology Letters
Xijuan Ren, Xuemin Zhang, Xingzhuang Ma, Hui Liu, Li Wang
BACKGROUND: TPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear. OBJECTIVE: To explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs. METHODS: Male SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0...
May 6, 2023: Toxicology Letters
Beom Hee Kim, Hyun Chul Koh
CK2 regulates receptor-mediated mitophagy that removes damaged mitochondria. The PINK1/Parkin pathways also involve mitochondrial clearance through mitophagy. However, it is not clear whether CK2 regulates PINK1/Parkin-dependent mitophagy in response to stress. Rotenone treatment showed a decrease of FUNDC1 expression in the mitochondrial fraction of SH-SY5Y and HeLa cells, but an increase of PINK1/Parkin expression only in SH-SY5Y cells. Interestingly, CK2 inhibition increased mitochondrial LC3II expression in rotenone-treated HeLa cells, whereas it decreased in SH-SY5Y cells, indicating that CK2 mediates rotenone-induced mitophagy in dopaminergic neurons...
May 6, 2023: Toxicology Letters
Morgana Brondani, Ana Cristina Roginski, Rafael Teixeira Ribeiro, Maria Paula de Medeiros, Chrístofer Ian Hernandez Hoffmann, Moacir Wajner, Guilhian Leipnitz, Bianca Seminotti
Redox homeostasis, mitochondrial functions, and mitochondria-endoplasmic reticulum (ER) communication were evaluated in the striatum of rats after 3-nitropropionic acid (3-NP) administration, a recognized chemical model of Huntington's disease (HD). 3-NP impaired redox homeostasis by increasing malondialdehyde levels at 28 days, decreasing glutathione (GSH) concentrations at 21 and 28 days, and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione S-transferase at 7, 21, and 28 days, catalase at 21 days, and glutathione reductase at 21 and 28 days...
April 26, 2023: Toxicology Letters
Chenpeng Zhu, Weikuan Gu, Dianjun Sun, Wei Wei
The renin-angiotensin system (RAS) is an important fluid regulation system in the body, and excessive activation of the circulatory or local RAS can increase blood pressure (BP). Excess fluoride can increase BP, although the underlying mechanism related to activation of the RAS remains unclear. Thus, the aim of this study was to elucidate the role of the RAS in fluoride-induced hypertension. Markers of the circulating and local RASs related to pathological changes to the kidneys, myocardium, and aorta were measured...
April 25, 2023: Toxicology Letters
Qi Zhang, Jing Ye, Zhaofeng Zhang, Yongkang Hu, Xian Wang, Wenjuan Jiang, Xinlong Guo, Langqun Chen, Siyu Cheng, Jian Li, Liang Zhang
Aristolochic acid I (AAI) can cause nephrotoxicity and is characterized by interstitial fibrosis. The C3a/C3aR axis of macrophages and matrix metalloproteinase-9 (MMP-9) play important roles in fibrosis, but whether they are involved in AAI-induced renal interstitial fibrosis and are related remains to be elucidated. In this study, we investigated whether C3a/C3aR axis of macrophages promotes renal interstitial fibrosis by regulating MMP-9 in aristolochic acid nephropathy (AAN). Intraperitoneal injection of AAI for 28 days successfully induced AAN in C57bl/6 mice...
April 19, 2023: Toxicology Letters
Anja Franken, Barbara Sylvia Bosch, Cornelius Johannes Van der Merwe, Jeanetta Du Plessis, Johannes Lodewykus Du Plessis
Halogenated platinum salts are known respiratory sensitizers in the workplace, and occupational exposure to platinum via the respiratory system and skin has been reported. The aim of this study was to compare the permeability and skin retention of potassium hexachloroplatinate to previously published data of potassium tetrachloroplatinate. Experiments were performed using female Caucasian skin and Franz diffusion cells with the application of 0.3mg Pt/mL in the donor solution for 24-hours. After 8-hours of exposure, 1...
April 17, 2023: Toxicology Letters
Aditya R Kolli
Nicotine from inhaled combustible cigarette smoke is delivered rapidly to the brain, and sufficient unbound nicotine concentrations exert pharmacological effects. In addition to nicotine, combustible cigarette smoke also contains a significant number of toxicants that trigger perturbations, leading to an altered steady state due to differential expression of proteins. In this study, a physiologically based pharmacokinetic (PBPK) model for inhaled nicotine was used to simulate the influence of lysosomal change-driven tissue retention and plasma protein binding levels on nicotine pharmacokinetics (PK)...
April 15, 2023: Toxicology Letters
Ji-Ming Sha, Ren-Quan Zhang, Xian-Chen Wang, Yang Zhou, Kai Song, He Sun, Bin Tu, Hui Tao
Epigenetic has been implicated in pulmonary fibrosis. However, there is limited information regarding the biological role of the epigenetic reader MeCP2 in pulmonary fibrosis. The aim of this study was to investigate the role of MeCP2 and its target WIF1 in pulmonary fibrosis. The pathological changes and collagen depositions was analyzed by H&E, Masson's Trichrome Staining and Sirius Red staining. MeCP2, WIF1, α-SMA, Wnt1, β-catenin, and collagen I expression were analyzed by western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, respectively...
April 13, 2023: Toxicology Letters
Barbara Füzi, Neann Mathai, Johannes Kirchmair, Gerhard F Ecker
In silico methods are essential to the safety evaluation of chemicals. Computational risk assessment offers several approaches, with data science and knowledge-based methods becoming an increasingly important sub-group. One of the substantial attributes of data science is that it allows using existing data to find correlations, build strong hypotheses, and create new, valuable knowledge that may help to reduce the number of resource intensive experiments. In choosing a suitable method for toxicity prediction, the available data and desired toxicity endpoint are two essential factors to consider...
April 13, 2023: Toxicology Letters
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