The objective of the current study was to establish an in vitro screen and a highly sensitive analytical assay to delineate key physicochemical properties that favor compound bioaccumulation in the L3 life stage of a Haemonchus contortus isolate. Time-dependent studies revealed that absorption and elimination kinetics during the first 6 hr of exposure were sufficient to achieve maximum bioaccumulation for the majority of compounds tested. In subsequent studies, the larvae were incubated for 6 hr in a medium containing 146 compounds (5 μM initial concentration), including both human and veterinary medicines, characterized by a broad range of physicochemical properties. Bioaccumulation of the compounds by the nematodes was determined, and multiple physicochemical descriptors were selected for correlation. Data analysis using Bayes classification model and partial least-square regression revealed that clogD7.4, rotatable bond, E-state, and hydrogen bond donor each correlated with compound bioaccumulation in H. contortus L3. The finding that lipophilicity was critical for transcuticle compound permeation was consistent with previous studies in other parasitic species and in adult H. contortus . The finding of additional physicochemical properties that contribute to compound conformational flexibility, polarity, and electrotopological state shed light on the mechanisms governing transcuticle permeation. The relatively poor correlation between transcuticle and transmembrane permeation indicated the distinct mechanisms of compound permeation, likely due to the different constituents, and their contributions to overall transport function, of the lipid membranes and the porous collagen barrier of the nematode cuticle. Our study, for the first time, establishes a high-throughput screen for compound bioaccumulation in a parasitic nematode and further elucidates physicochemical factors governing transcuticular permeation of compounds. Application of this methodology will help explain the basis for discrepancies observed in receptor binding and whole organism potency assays and facilitate incorporation of drug delivery principles in the design of candidate anthelmintics.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1645/14-556.1 | DOI Listing |
Sci Total Environ
January 2025
International Joint Research Centre for Persistent Toxic Substances (IJRC-PTS), College of Environmental Science and Engineering, Dalian Maritime University, Dalian 116026, PR China. Electronic address:
Although the concept of bioaccumulation for novel brominated flame retardants (NBFRs) is clear, the process and interfering factors of bioaccumulation are still not fully understood. The present study comprehensively evaluated the occurrence, transfer and interfering factors of NBFRs in a marine food web to provide new thought and perspective for the bioaccumulation of these compounds. The occurrence of 17 NBFRs were determined from 8 water, 8 sediment and 303 organism samples collected from Dalian Bay, China.
View Article and Find Full Text PDFToxics
December 2024
Key Laboratory of Ministry of Education for Water Quality Security and Protection in Pearl River Delta, School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China.
Recently, 7-diethylamino-4-methylcoumarin (DEAMC) has been identified as a potent antiandrogenic compound in the surface water; however, little is known about the antiandrogenic potentials of other synthetic coumarins and their occurrence in the aquatic ecosystem. In this study, for the first time, we observed that 7-dimethylamino-4-methylcoumarin (DAMC) elicited androgen receptor (AR) antagonistic activity with a 50% inhibitory concentration (IC) of 1.46 µM, which is 14.
View Article and Find Full Text PDFMicroorganisms
December 2024
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Mexico City 04510, Mexico.
Polycyclic aromatic hydrocarbons (PAHs) are toxic organic compounds produced during the incomplete combustion of organic materials and are commonly found in the environment due to anthropogenic activities such as industrial and vehicular emissions as well as natural sources, mainly volcanic eruptions and forest fires. PAHs are well known for their bioaccumulative capacity and environmental persistence, raising concerns due to their adverse effects on human health, including their carcinogenic potential. In recent years, bioremediation has emerged as a promising, effective, and sustainable solution for the degradation of PAHs in contaminated environments.
View Article and Find Full Text PDFMolecules
December 2024
Institute of Meteorology and Water Management, National Research Institute, Waszyngtona 42, 81-342 Gdynia, Poland.
In this study, the results of a comprehensive assessment of the variability in the occurrence of ten perfluorinated compounds (PFAS) in fish tissues originating from 2014 to 2019 from six fisheries in the Baltic Sea are presented. A total of 360 fish samples of three species (perch, herring and flatfish) were analysed. For the determination of PFAS, both linear and branched stereoisomers, LC-ESI-MS/MS technique preceded by simultaneous SPE isolation was validated and applied.
View Article and Find Full Text PDFCells
December 2024
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, India.
The quest for cleaner and sustainable energy sources is crucial, considering the current scenario of a steep rise in energy consumption and the fuel crisis, exacerbated by diminishing fossil fuel reserves and rising pollutants. In particular, the bioaccumulation of hazardous substances like trivalent chromium has not only disrupted the fragile equilibrium of the ecological system but also poses significant health hazards to humans. Microalgae emerged as a promising solution for achieving sustainability due to their ability to remediate contaminants and produce greener alternatives such as biofuels.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!