Jolly, Carol E. Douglas, Oisin Kamalian, Laleh Jenkins, Rosalind E. Beckett, Alison J. Penman, Sophie L. Williams, Dominic P. Monshouwer, Mario Simic, Damir Snoeys, Jan
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Published in
Toxicology and Applied Pharmacology
• Metabolic modification has been adapted to identify delayed (weeks) mitochondrial dysfunction. • Fialuridine induces delayed mitochondrial dysfunction and toxicity at physiologically relevant exposures. • Inhibition of mitochondrial replication leads to decreased oxidative phosphorylation before cell death. • HepaRG cells are a more suitable mode...
Baralić, Katarina Jorgovanović, Dragica Živančević, Katarina Antonijević Miljaković, Evica Antonijević, Biljana Buha Djordjevic, Aleksandra Ćurčić, Marijana Đukić-Ćosić, Danijela
Published in
Toxicology and Applied Pharmacology
• Lopinavir/ritonavir affect genes involved in immune system and lipid metabolism • Cardiotoxicity, inflammation, dyslipidemias – lopinavir/ritonavir therapy main risk • Chloroquine/azithromycin interact with genes linked to cytokine regulation • Chloroquine affects two genes more than hydroxychloroquine (BCL2L1 and CYP3A4) • CVD, GIT, skin disease...
Larsen, Michele Campaigne Almeldin, Ahmed Tong, Tiegang Rondelli, Catherine M Maguire, Meghan Jaskula-Sztul, Renata Jefcoate, Colin R
Published in
Toxicology and applied pharmacology
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are metabolized to carcinogenic dihydrodiol epoxides (PAHDE) by cytochrome P450 1B1 (CYP1B1). This metabolism occurs in bone marrow (BM) mesenchymal stem cells (MSC), which sustain hematopoietic stem and progenitor cells (HSPC). In BM, CYP1B1-mediated metabolism of 7, 12-dimethy...
Park, Eun-Jung Seong, Eunsol Kang, Min-Sung Lee, Gwang-Hee Kim, Dong-Wan Han, Ji-Seok Lim, Hyun-Ji Lee, Seung Hyeun Han, Hyoung-Yun
Published in
Toxicology and applied pharmacology
Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic re...
Ridder, Bradley J. Leishman, Derek J. Bridgland-Taylor, Matthew Samieegohar, Mohammadreza Han, Xiaomei Wu, Wendy W. Randolph, Aaron Tran, Phu Sheng, Jiansong Danker, Timm
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Published in
Toxicology and Applied Pharmacology
Ridder, Bradley J. Leishman, Derek J. Bridgland-Taylor, Matthew Samieegohar, Mohammadreza Han, Xiaomei Wu, Wendy W. Randolph, Aaron Tran, Phu Sheng, Jiansong Danker, Timm
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Published in
Toxicology and Applied Pharmacology
• hERG potency/safety margin is a widely used nonclinical cardiac safety strategy. • A new regulatory paradigm promotes the integration of nonclinical and clinical data. • Lack of uncertainty quantification hindered using hERG potency in the new paradigm. • A systematic method was established to address this limitation. • Analysis supports using di...
Morissette, Pierre Polak, Sebastian Chain, Anne Zhai, Jin Imredy, John P Wildey, Mary Jo Travis, Jeffrey Fitzgerald, Kevin Fanelli, Patrick Passini, Elisa
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Toxicology and applied pharmacology
Human-based in silico models are emerging as important tools to study the effects of integrating inward and outward ion channel currents to predict clinical proarrhythmic risk. The aims of this study were 2-fold: 1) Evaluate the capacity of an in silico model to predict QTc interval prolongation in the in vivo anesthetized cardiovascular guinea pig...
Nault, Rance Bals, Bryan Teymouri, Farzaneh Black, Michael B Andersen, Melvin E McMullen, Patrick D Krishnan, Seetha Kuravadi, Nagesh Paul, Neetha Kumar, Santhosh
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Published in
Toxicology and applied pharmacology
Acetamide (CAS 60-35-5) is detected in common foods. Chronic rodent bioassays led to its classification as a group 2B possible human carcinogen due to the induction of liver tumors in rats. We used a toxicogenomics approach in Wistar rats gavaged daily for 7 or 28 days at doses of 300 to 1500 mg/kg/day (mkd) to determine a point of departure (POD) ...
Reed, Lindsay Indra, Radek Mrizova, Iveta Moserova, Michaela Schmeiser, Heinz H Wolf, C Roland Henderson, Colin J Stiborova, Marie Phillips, David H Arlt, Volker M
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Toxicology and applied pharmacology
The anticancer drug ellipticine exerts its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. The present study has examined the role of cytochrome P450 oxidoreductase (POR) and cytochrome b5 (Cyb5), electron donors to P450 enzymes, in the CYP-mediated metabolism and disposition of ellipticine in vivo. We used Hepatic Re...
Yang, Cheng-Wei Chang, Hsin-Yu Lee, Yue-Zhi Hsu, Hsing-Yu Lee, Shiow-Ju
Published in
Toxicology and applied pharmacology
Cardenolides are plant-derived toxic substances. Their cytotoxicity and the underlying mechanistic signaling axes have been extensively documented, but only a few anti-viral activities of cardenolides and the associated signaling pathways have been reported. Previously, we reported that a variety of cardenolides impart anti-transmissible gastroente...
