Over the last decade, significant progress been made in elucidating the role of membrane transporters in altering drug disposition, with important toxicological consequences due to changes in localized concentrations of compounds. The topic of "Transporters and Toxicity" was recently highlighted as a scientific session at the International Transporter Consortium (ITC) Workshop 4 in 2021. The current white paper is not intended to be an extensive review on the topic of transporters and toxicity but an opportunity to highlight aspects of the role of transporters in various toxicities with clinically relevant implications as covered during the session. This includes a review of the role of solute carrier transporters in anticancer drug-induced organ injury, transporters as key players in organ barrier function, and the role of transporters in metal/metalloid toxicity.
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http://dx.doi.org/10.1002/cpt.2638 | DOI Listing |
Pharmacotherapy
December 2024
Texas Children's Cancer and Hematology Centers, Houston, Texas, USA.
Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.
Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.
Part Fibre Toxicol
December 2024
Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, P.O. Box 951679, Los Angeles, CA, 90095, USA.
Background: Exposure to air pollution is associated with worldwide morbidity and mortality. Diesel exhaust (DE) emissions are important contributors which induce vascular inflammation and metabolic disturbances by unknown mechanisms. We aimed to determine molecular pathways activated by DE in the liver that could be responsible for its cardiometabolic toxicity.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
School of Public Health, Guangzhou Medical University, Guangzhou 511436, China. Electronic address:
The burden of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized products on human health can no longer be ignored due to the detection types and concentrations in the environment continue to increase. Environmental ozone (O) and ultraviolet A (UVA) may induce ozonation and photoaging of 6PPD to produce toxic products. However, the impact of specific environmental conditions on the aging and toxic effects of 6PPD is unclear.
View Article and Find Full Text PDFSci Rep
December 2024
Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Jagiellońska 28, 40-032, Katowice, Poland.
Studies of in situ plant response and adaptation to complex environmental stresses, are crucial for understanding the mechanisms of formation and functioning of ecosystems of anthropogenically transformed habitats. We study short- and long-term responses of photosynthetic apparatus (PSA) and anti-oxidant capacity to complex abiotic stresses of common plants Calamagrostis epigejos and Solidago gigantea in semi-natural (C) and heavy metal contaminated habitats (LZ). We found significant differences in leaf pigment content between both plant species growing on LZ plots and their respective C populations.
View Article and Find Full Text PDFSci Rep
December 2024
Division of Plant Science and Technology, University of Missouri, Columbia, MO, 65211, USA.
The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, has evolved resistance to nearly every management tactic utilized in the field. This study investigated the resistance mechanisms in a WCR strain resistant to the Bacillus thuringiensis (Bt) protein eCry3.1Ab using dsRNA to knockdown WCR midgut genes previously documented to be associated with the resistance.
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