The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites. We used commercially available software to predict metabolites of 50 parent compounds, out of which 38 chemicals are known to have estrogenic metabolites, and 12 compounds and their metabolites are negative for estrogenic activity. Three ER QSAR models were used to determine potential estrogen bioactivity of the parent compounds and predicted metabolites, the outputs of the models were averaged, and the chemicals were then ranked based on the total estrogenicity of the parent chemical and metabolites. The metabolite prediction software correctly identified known estrogenic metabolites for 26 out of 27 parent chemicals with associated metabolite data, and 39 out of 46 estrogenic metabolites were predicted as potential biotransformation products derived from the parent chemical. The QSAR models estimated stronger estrogenic activity for the majority of the known estrogenic metabolites compared to their parent chemicals. Finally, the three models identified a similar set of parent compounds as top ranked chemicals based on the estrogenicity of putative metabolites. This proposed in silico approach is an inexpensive and rapid strategy for the detection of chemicals with estrogenic metabolites and may reduce potential false negative results from in vitro assays.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/acs.chemrestox.6b00079 | DOI Listing |
Ann Med
December 2025
Department of Gynecology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
As one of the three major malignant tumors in women, the morbidity of endometrial cancer is second only to that of cervical cancer and is increasing yearly. Its etiological mechanism is not clear, and the risk factors are numerous and common and are closely related to obesity, hypertension, diabetes, etc. The gut microbiota has many strains, which play a considerable part in normal digestion and absorption in the human body and the regulation of the immune response.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, PR China. Electronic address:
Differential distribution of neonicotinoids (NEOs) in albumen, yolk, and eggshell is a critical factor influencing their bio-accumulative behavior and the subsequent human health risks. However, there is currently no relevant research available. We collected 62 egg samples from 31 sampling sites across China and analyzed the concentrations and characteristics of 12 parents NEOs (p-NEOs) and 8 metabolites NEOs (m-NEOs) in albumen, yolk, and eggshell.
View Article and Find Full Text PDFJ Am Nutr Assoc
January 2025
School of Medicine, University of Granada, Granada, Spain.
Breast cancer (BC) is one of the leading causes of death and morbidity among women worldwide. Epidemiologic evidence shows that the risk of BC and other chronic diseases decreases as the proportion of whole plant foods increases, while the proportion of animal foods (fish, meat, poultry, eggs, seafood, and dairy products) and non-whole plant foods (e.g.
View Article and Find Full Text PDFPharm Res
January 2025
Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA.
Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Medical Biochemistry, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey.
The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!