Environmental Pollution, Год журнала: 2024, Номер unknown, С. 125323 - 125323
Опубликована: Ноя. 1, 2024
Язык: Английский
Environmental Research, Год журнала: 2025, Номер 276, С. 121530 - 121530
Опубликована: Апрель 5, 2025
Язык: Английский
Процитировано
0
Toxics, Год журнала: 2024, Номер 12(3), С. 183 - 183
Опубликована: Фев. 28, 2024
Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition their impact on human health environment has stimulated attention research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, industry representatives, collaborating develop robust methodologies guidelines for assessing these disruptors. A key aspect efforts is development standardized testing protocols that aim provide consistent reliable methods identifying characterizing endocrine When evaluating potential activity chemicals, no single test capable detecting all relevant agents. The battery approach designed reduce risk false negative results compounds with toxic potential. weight-of-evidence therefore necessary disruptor evaluation. This considers various types data from multiple sources, overall strength, consistency, reliability evidence. OECD highly regarded scientific rigor, transparency, consensus-based process. It crucial explore new can effectively evaluate risks associated Integrating into a comprehensive framework will enhance assessments facilitate informed decisions regarding regulation management substances, ensuring protection adverse effects.
Язык: Английский
Процитировано
2
Journal of Hazardous Materials, Год журнала: 2024, Номер 474, С. 134721 - 134721
Опубликована: Май 28, 2024
The new challenges in toxicology demand novel and innovative vitro approaches for deriving points of departure (PODs) determining the mode action (MOA) chemicals. Therefore, aim this original study was to couple studies with untargeted metabolomics model concentration-response extra- intracellular metabolome data on human HepaRG cells treated 48 h three pyrrolizidine alkaloids (PAs): heliotrine, retrorsine lasiocarpine. Modeling revealed that PAs induced various monotonic and, importantly, biphasic curves metabolite content. Based unannotated metabolites, endometabolome more sensitive than exometabolome terms metabolomic effects, benchmark concentrations (BMCs) confirmed lasiocarpine most hepatotoxic PA. Regarding its MOA, impairment lipid metabolism highlighted at a very low BMC (first quartile, 0.003 µM). Moreover, results targets bile acids, as well amino acid steroid metabolisms. Analysis endometabolome, based coupling PODs, gave encouraging ranking toxins according their effects. approach is promising tool next-generation risk assessment, readily applicable broad range compounds toxic endpoints.
Язык: Английский
Процитировано
2
Food Bioscience, Год журнала: 2024, Номер 60, С. 104482 - 104482
Опубликована: Май 31, 2024
Язык: Английский
Процитировано
2
Environment International, Год журнала: 2024, Номер 190, С. 108926 - 108926
Опубликована: Авг. 1, 2024
Pregnane X receptor (PXR) is a heterologous biosensor that involved in the metabolic pathway of environmental pollutants, regulating transcription genes biotransformation. There are significant differences selectivity and specificity organic pollutants (OPs) toward polar bear PXR (pbPXR) human (hPXR), but detailed dynamical characteristics their interactions unclear. Homology Modeling, molecular docking, dynamics simulation, free energy calculation were used to analyze recognition pbPXR hPXR by three OPs: BPA, chlordane toxaphene. Comparing interaction patterns along with binding these OPs revealed although interact similar OPs, have different effects on internal hPXR. This results alterations key residues near Leu209, Met243, Phe288, Met323, His407 thereby influencing energy. Non-polar interactions, especially van der Waals found be dominating factors interacting PXRs. The region surrounding facilitates hydrophobic contacts PXR, which crucial for selective activation PXRs species OPs. These findings guidance understanding impacts endocrine disruptors organisms.
Язык: Английский
Процитировано
2
Current Molecular Pharmacology, Год журнала: 2023, Номер 17
Опубликована: Окт. 19, 2023
Abstract: The incidence of nonalcoholic fatty liver disease (NAFLD) has been rising worldwide in parallel with diabetes and metabolic syndrome. NAFLD refers to a spectrum abnormalities variable course, ranging from (NAFL) steatohepatitis (NASH), eventually leading cirrhosis hepatocellular carcinoma. Pregnane X receptor (PXR), member the nuclear superfamily, plays prominent part regulation endogenous genes NAFLD. Recent studies have suggested that PXR therapeutic potential for NAFLD, yet relationship between remains controversial. In this review, is proposed play dual role development progression Its activation will aggravate steatosis liver, reduce inflammatory response, prevent fibrosis. addition, interactions PXR, substance metabolism, inflammation, fibrosis, gut microbiota non-alcoholic were elucidated. Due limited options, better understanding contribution pathogenesis should facilitate design innovative drugs targeting
Язык: Английский
Процитировано
3
Environmental Pollution, Год журнала: 2024, Номер unknown, С. 125323 - 125323
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
0