Knowledge of inter-strain and inter-gender differences in drug metabolism studies is important for animal selection in pharmacokinetic and toxicological studies. The effects of rat strain and gender in metabolism were investigated in Sprague Dawley (SD) and Wister Han (WH) rats based on the hepatocyte metabolic profiles of 14 small molecule drugs. Similarities were found between the hepatocyte metabolic clearances of SD and WH strains, suggesting that only one strain can be confidently used for the evaluation of hepatic clearance. Neither strain of rat was preferable over the other to cover human metabolites. Higher similarities in metabolic pathways were found between the same gender than the same strain. Differences in metabolite identities, metabolite formation rates and potential biotransformation pathways were observed between SD and WH rat strains. Eleven metabolites from six drugs were "disproportionally" formed between SD and WH rats. The use of a specific rat strain model and gender for ADME and toxicity testing should, therefore, be carefully considered as metabolic profiles may differ, even though metabolic clearance was similar between SD and WH rats.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/00498254.2020.1795949 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Study of antiplasmodial activity, toxicity, pharmacokinetic profiles of n-methyl-isatin (CHISACN) derivative.
Exp Parasitol
January 2025
Post-graduate Program in Studies in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa, PB, Brazil; Laboratory of Toxicological Tests, Federal University of Paraíba, João Pessoa, PB, Brazil; Post-graduate Program in Studies in Development and Technological Innovation in Medicines, Federal University of Paraíba, João Pessoa, PB, Brazil.
One of the main factors that have made it difficult to control malaria is the large number of parasites that are resistant to the usual antimalarial drugs. Therefore, the development of new drugs that are more effective and with low toxicity for humans is necessary. In this work, we evaluated the adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-yl) acrylonitrile, also called CHISACN, as a potential antimalarial through in vitro studies, and evaluated its effects in silico and in vivo toxicology.
View Article and Find Full Text PDFChewing-Activated TRPV4/PIEZO1--Zn Axes in a Rat Periodontal Complex.
J Dent Res
January 2025
Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA, USA.
The upstream mechanobiological pathways that regulate the downstream mineralization rates in periodontal tissues are limitedly understood. Herein, we spatially colocalized and correlated compression and tension strain profiles with the expressions of mechanosensory ion channels (MS-ion) TRPV4 and PIEZO1, biometal zinc, mitochondrial function marker (), cell senescence indicator (), and oxygen status marker hypoxia-inducible factor-1α () in rats fed hard and soft foods. The observed zinc and related cellular homeostasis in vivo were ascertained by TRPV4 and PIEZO1 agonists and antagonists on human periodontal ligament fibroblasts ex vivo.
View Article and Find Full Text PDFOkra seed polysaccharides mitigate neuroinflammation and cognitive impairment via modulation of Nrf2/HO-1, HMGB1/RAGE/TLR4/NF-κB, NLRP3/Caspase-1, JAK-2/STAT-3, AMPK/SIRT1/m-TOR, PI3K/AKT/CREB/BDNF/TrkB and PERK/CHOP/Bcl-2 axes.
Int Immunopharmacol
January 2025
Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA. Electronic address:
Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits.
View Article and Find Full Text PDFEstablishment of Recombinant Gene Rabies Virus SRV and Identification of Its Biological Characteristics.
Viruses
December 2024
School of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China.
Canids act as a crucial intermediary in the transmission of rabies and , serving as co-infection hosts and pathogen carriers for both rabies and hydatid disease (HD) transmitted from animals to humans. Therefore, an effective and efficient bivalent oral vaccine for preventing HD and rabies is urgently required to reduce economic losses in husbandry resulting from rabies and HD. In this study, a full-length plasmid (pcDNA4-NPM+G+EgM123+eGFP+L) carrying the gene and fluorescence reporter genes of eGFP and four auxiliary transfection plasmids of rabies virus SRV (pcDNA4-N, pcDNA4-P, pcDNA4-G, pcDNA-L) were established by reverse genetics approaches and co-transfected to BSR cells by electrotransfection.
View Article and Find Full Text PDFResilience of Spontaneously Hypertensive Rats to Secondary Insults After Traumatic Brain Injury: Immediate Seizures, Survival, and Stress Response.
Int J Mol Sci
January 2025
Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic-pituitary-adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!