journal
https://read.qxmd.com/read/38761188/two-novel-in-vitro-assays-to-screen-chemicals-for-their-capacity-to-inhibit-thyroid-hormone-transmembrane-transporter-proteins-oatp1c1-and-oat4
#1
JOURNAL ARTICLE
Fabian Wagenaars, Peter Cenijn, Zhongli Chen, Marcel Meima, Martin Scholze, Timo Hamers
Early brain development depends on adequate transport of thyroid hormones (THs) from the maternal circulation to the fetus. To reach the fetal brain, THs have to cross several physiological barriers, including the placenta, blood-brain-barrier and blood-cerebrospinal fluid-barrier. Transport across these barriers is facilitated by thyroid hormone transmembrane transporters (THTMTs). Some endocrine disrupting chemicals (EDCs) can interfere with the transport of THs by THTMTs. To screen chemicals for their capacity to disrupt THTMT facilitated TH transport, in vitro screening assays are required...
May 18, 2024: Archives of Toxicology
https://read.qxmd.com/read/38758407/molecular-mechanisms-of-environmental-pollutant-induced-cartilage-damage-from-developmental-disorders-to-osteoarthritis
#2
REVIEW
Anatoly V Skalny, Michael Aschner, Feng Zhang, Xiong Guo, Aleksandra Buha Djordevic, Tatiana I Sotnikova, Tatiana V Korobeinikova, Jose L Domingo, Sandra H P Farsky, Alexey A Tinkov
The objective of the present study was to review the molecular mechanisms of the adverse effects of environmental pollutants on chondrocytes and extracellular matrix (ECM). Existing data demonstrate that both heavy metals, including cadmium (Cd), lead (Pb), and arsenic (As), as well as organic pollutants, including polychlorinated dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCB), bisphenol A, phthalates, polycyclic aromatic hydrocarbons (PAH), pesticides, and certain other organic pollutants that target cartilage ontogeny and functioning...
May 17, 2024: Archives of Toxicology
https://read.qxmd.com/read/38758406/screening-for-ferroptosis-genes-related-to-endometrial-carcinoma-and-predicting-of-targeted-drugs-based-on-bioinformatics
#3
JOURNAL ARTICLE
Rui Wang, Wei Lang, Qian Xue, Le Zhang, Yunzhu Xujia, Chaofan Wang, Xin Fang, Shidi Gao, Li Guo
Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways...
May 17, 2024: Archives of Toxicology
https://read.qxmd.com/read/38755481/from-hazard-to-risk-prioritization-a-case-study-to-predict-drug-induced-cholestasis-using-physiologically-based-kinetic-modeling
#4
JOURNAL ARTICLE
Véronique M P de Bruijn, Ivonne M C M Rietjens
Cholestasis is characterized by hepatic accumulation of bile acids. Clinical manifestation of cholestasis only occurs in a small proportion of exposed individuals. The present study aims to develop a new approach methodology (NAM) to predict drug-induced cholestasis as a result of drug-induced hepatic bile acid efflux inhibition and the resulting bile acid accumulation. To this end, hepatic concentrations of a panel of drugs were predicted by a generic physiologically based kinetic (PBK) drug model. Their effects on hepatic bile acid efflux were incorporated in a PBK model for bile acids...
May 17, 2024: Archives of Toxicology
https://read.qxmd.com/read/38755480/mechanistic-safety-assessment-via-multi-omic-characterisation-of-systemic-pathway-perturbations-following-in-vivo-mat2a-inhibition
#5
JOURNAL ARTICLE
Valentina Fogal, Filippos Michopoulos, Andrew F Jarnuczak, Ghaith M Hamza, Stephanie Harlfinger, Paul Davey, Heather Hulme, Stephen J Atkinson, Piotr Gabrowski, Tony Cheung, Michael Grondine, Clare Hoover, Jonathan Rose, Chandler Bray, Alison J Foster, Sean Askin, Muntasir Mamun Majumder, Paul Fitzpatrick, Eric Miele, Ruth Macdonald, Hector C Keun, Muireann Coen
The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine...
May 17, 2024: Archives of Toxicology
https://read.qxmd.com/read/38753188/associations-among-global-long-interspersed-nuclear-element-1-dna-methylation-metal-exposure-and-chronic-kidney-disease
#6
JOURNAL ARTICLE
Yu-Mei Hsueh, Mei-Chieh Chen, Ying-Chin Lin, Chih-Yin Wu, Horng-Sheng Shiue, Sheng-Lun Hsu, Hsi-Hsien Chen, Ya-Li Huang
Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed...
May 16, 2024: Archives of Toxicology
https://read.qxmd.com/read/38753187/formation-of-functional-extended-bile-canaliculi-and-increased-bile-acid-production-in-sandwich-cultured-human-cryopreserved-hepatocytes-using-commercially-available-culture-medium
#7
JOURNAL ARTICLE
Shinichiro Horiuchi, Yukie Kuroda, Ryota Oyafuso, Yuji Komizu, Kazuya Maeda, Seiichi Ishida
Drug-induced cholestasis results in drug discontinuation and market withdrawal, and the prediction of cholestasis risk is critical in the early stages of drug development. Animal tests and membrane vesicle assay are currently being conducted to assess the risk of cholestasis in the preclinical stage. However, these methods have drawbacks, such as species differences with humans and difficulties in evaluating the effects of drug metabolism and other transporters, implying the need for a cholestasis risk assessment system using human hepatocytes...
May 16, 2024: Archives of Toxicology
https://read.qxmd.com/read/38748041/cannabidivarin-and-cannabigerol-induce-unfolded-protein-response-and-angiogenesis-dysregulation-in-placental-trophoblast-htr-8-svneo-cells
#8
JOURNAL ARTICLE
Patrícia Alves, Cristina Amaral, Marina S Gonçalves, Natércia Teixeira, Georgina Correia-da-Silva
Cannabidivarin (CBDV) and cannabigerol (CBG) are minor phytocannabinoids from Cannabis sativa, whose health benefits have been reported. However, studies about the impact of these cannabinoids on fundamental cellular processes in placentation are scarce. Placental development involves physiological endoplasmic reticulum (ER) stress, however when exacerbated it can lead to altered angiogenesis and pregnancy disorders, such as intrauterine growth restriction and preeclampsia. In this work, the effects of CBDV and CBG (1-10 µM) on placental extravillous trophoblasts were studied, using the in vitro model HTR-8/SVneo cells...
May 15, 2024: Archives of Toxicology
https://read.qxmd.com/read/38744709/the-role-of-cellular-senescence-in-neurodegenerative-diseases
#9
REVIEW
Yating Wang, Kamil Kuca, Li You, Eugenie Nepovimova, Zbynek Heger, Marian Valko, Vojtech Adam, Qinghua Wu, Klaudia Jomova
Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activity in in vitro and in vivo ND models...
May 15, 2024: Archives of Toxicology
https://read.qxmd.com/read/38743292/the-entactogen-3-4-methylenedioxymethamphetamine-mdma-ecstasy-as-a-treatment-aid-in-psychotherapy-and-its-safety-concerns
#10
REVIEW
Brian A Baldo
The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties...
May 14, 2024: Archives of Toxicology
https://read.qxmd.com/read/38740588/investigation-of-parenteral-nutrition-induced-hepatotoxicity-using-human-liver-spheroid-co-cultures
#11
JOURNAL ARTICLE
Milos Mihajlovic, Sybren De Boever, Andrés Tabernilla, Ellen Callewaert, Julen Sanz-Serrano, Anouk Verhoeven, Amy Maerten, Zenzi Rosseel, Elisabeth De Waele, Mathieu Vinken
Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN...
May 14, 2024: Archives of Toxicology
https://read.qxmd.com/read/38739308/carbon-nanotubes-conjugated-with-cisplatin-activate-different-apoptosis-signaling-pathways-in-2d-and-3d-spheroid-triple-negative-breast-cancer-cell-cultures-a-comparative-study
#12
JOURNAL ARTICLE
Madalina Andreea Badea, Mihaela Balas, Daniela Ionita, Anca Dinischiotu
The type of experimental model for the in vitro testing of drug formulations efficiency represents an important tool in cancer biology, with great attention being granted to three-dimensional (3D) cultures as these offer a closer approximation of the clinical sensitivity of drugs. In this study, the effects induced by carboxyl-functionalized single-walled carbon nanotubes complexed with cisplatin (SWCNT-COOH-CDDP) and free components (SWCNT-COOH and CDDP) were compared between conventional 2D- and 3D-spheroid cultures of human breast cancer cells...
May 13, 2024: Archives of Toxicology
https://read.qxmd.com/read/38735004/investigation-of-the-intrinsic-cannabinoid-activity-of-hemp-derived-and-semisynthetic-cannabinoids-with-%C3%AE-arrestin2-recruitment-assays-and-how-this-matters-for-the-harm-potential-of-seized-drugs
#13
JOURNAL ARTICLE
Liesl K Janssens, Katleen Van Uytfanghe, Jeffrey B Williams, Kirk W Hering, Donna M Iula, Christophe P Stove
Cultivation of industrial low-Δ9 -tetrahydrocannabinol (Δ9 -THC) hemp has created an oversupply of cannabidiol (CBD)-rich products. The fact that phytocannabinoids, including CBD, can be used as precursors to synthetically produce a range of THC variants-potentially located in a legal loophole-has led to a diversification of cannabis recreational drug markets. 'Hemp-compliant', 'hemp-derived' and 'semisynthetic' cannabinoid products are emerging and being advertised as (legal) alternatives for Δ9 -THC...
May 12, 2024: Archives of Toxicology
https://read.qxmd.com/read/38722348/targeting-gut-microbiota-for-immunotherapy-of-diseases
#14
REVIEW
Ya-Jie Yu, Xiao-Dong Liu, Cai Liao, Rui Yu, Xin Wang, Ming Li, Yun Wang
With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs)...
May 9, 2024: Archives of Toxicology
https://read.qxmd.com/read/38722347/systematic-evaluation-of-high-throughput-pbk-modelling-strategies-for-the-prediction-of-intravenous-and-oral-pharmacokinetics-in-humans
#15
JOURNAL ARTICLE
René Geci, Domenico Gadaleta, Marina García de Lomana, Rita Ortega-Vallbona, Erika Colombo, Eva Serrano-Candelas, Alicia Paini, Lars Kuepfer, Stephan Schaller
Physiologically based kinetic (PBK) modelling offers a mechanistic basis for predicting the pharmaco-/toxicokinetics of compounds and thereby provides critical information for integrating toxicity and exposure data to replace animal testing with in vitro or in silico methods. However, traditional PBK modelling depends on animal and human data, which limits its usefulness for non-animal methods. To address this limitation, high-throughput PBK modelling aims to rely exclusively on in vitro and in silico data for model generation...
May 9, 2024: Archives of Toxicology
https://read.qxmd.com/read/38713375/lack-of-cyp3a4-protein-induction-despite-mrna-induction-in-primary-hepatocytes-exposed-to-rifabutin-as-a-possible-explanation-for-its-low-interaction-risk-in-vivo
#16
JOURNAL ARTICLE
Julie Nilles, Dirk Theile, Johanna Weiss, Walter E Haefeli, Stephanie Ruez
Rifampicin is a strong inducer of cytochrome P450 (CYP3A4) and P-glycoprotein (P-gp/ABCB1), leading to profound drug-drug interactions. In contrast, the chemically related rifabutin does not show such pronounced induction properties in vivo. The aim of our study was to conduct a comprehensive analysis of the different induction potentials of rifampicin and rifabutin in primary human hepatocytes and to analyze the mechanism of potential differences. Therefore, we evaluated CYP3A4/ABCB1 mRNA expression (polymerase chain reaction), CYP3A4/P-gp protein expression (immunoaffinity-liquid chromatography-mass spectrometry, IA-LC-MS/MS), CYP3A4 activity (testosterone hydroxylation), and considered intracellular drug uptake after treatment with increasing rifamycin concentrations (0...
May 7, 2024: Archives of Toxicology
https://read.qxmd.com/read/38704806/thresholds-of-adversity-for-endocrine-disrupting-substances-a-conceptual-case-study
#17
JOURNAL ARTICLE
Judy Choi, Stefanie Rotter, Vera Ritz, Carsten Kneuer, Philip Marx-Stoelting, Marize de Lourdes Marzo Solano, Angelika Oertel, Susanne Rudzok, Andrea Ziková-Kloas, Tewes Tralau, Andreas Hensel
For endocrine disrupting chemicals (EDC) the existence of "safe exposure levels", that is exposure levels that do not present an appreciable risk to human health is most controversially discussed, as is the existence of health-based reference values. Concerns have been especially raised that EDCs might not possess a threshold level such that no exposure level to EDCs can be considered safe. To explore whether or not threshold levels can be identified, we performed a screening exercise on 14 pesticidal and biocidal active substances previously identified as EDCs in the European Union...
May 5, 2024: Archives of Toxicology
https://read.qxmd.com/read/38704805/the-physiological-and-biochemical-basis-of-potency-thresholds-modeled-using-human-estrogen-receptor-alpha-implications-for-identifying-endocrine-disruptors
#18
JOURNAL ARTICLE
Christopher J Borgert, Lyle D Burgoon, John C Matthews
The endocrine system functions by interactions between ligands and receptors. Ligands exhibit potency for binding to and interacting with receptors. Potency is the product of affinity and efficacy. Potency and physiological concentration determine the ability of a ligand to produce physiological effects. The kinetic behavior of ligand-receptor interactions conforms to the laws of mass action. The laws of mass action define the relationship between the affinity of a ligand and the fraction of cognate receptors that it occupies at any physiological concentration...
May 5, 2024: Archives of Toxicology
https://read.qxmd.com/read/38703205/functional-metabolomics-characterizes-the-contribution-of-farnesoid-x-receptor-in-pyrrolizidine-alkaloid-induced-hepatic-sinusoidal-obstruction-syndrome
#19
JOURNAL ARTICLE
Aizhen Xiong, Longhui Lu, Kaiyuan Jiang, Xiaoning Wang, Yan Chen, Xunjiang Wang, Wei Zhang, Yuzheng Zhuge, Wendong Huang, Lujin Li, Qi Liao, Fan Yang, Ping Liu, Lili Ding, Zhengtao Wang, Li Yang
Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism...
May 4, 2024: Archives of Toxicology
https://read.qxmd.com/read/38695895/multi-omics-bioactivity-profile-based-chemical-grouping-and-read-across-a-case-study-with-daphnia-magna-and-azo-dyes
#20
JOURNAL ARTICLE
Hanna Gruszczynska, Rosemary E Barnett, Gavin R Lloyd, Ralf J M Weber, Thomas N Lawson, Jiarui Zhou, Elena Sostare, John K Colbourne, Mark R Viant
Grouping/read-across is widely used for predicting the toxicity of data-poor target substance(s) using data-rich source substance(s). While the chemical industry and the regulators recognise its benefits, registration dossiers are often rejected due to weak analogue/category justifications based largely on the structural similarity of source and target substances. Here we demonstrate how multi-omics measurements can improve confidence in grouping via a statistical assessment of the similarity of molecular effects...
May 2, 2024: Archives of Toxicology
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