Cholesterol and phospholipid content, and phospholipid composition (sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethaolamine) were assayed in rat liver microsomes during regeneration, foetal development and pregnancy. Cholesterol was assayed using Liebermann-Buchard reagent; the phospholipid extract was separated by thin-layer chromatography. While in pregnancy no changes were observed, during foetal development and liver regeneration there was a significative decrease of cholesterol/phospholipid ratio, and of phosphatidylcholine content. Moreover, in developing liver microsomes, there is also a significative increase of sphingomyelin and phosphatidylserine + phosphatidylinositol.
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Environ Int
December 2024
State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; Guangdong-Hong Kong-MacaoChina Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China. Electronic address:
The chlorinated paraffin (CP) monomer 1,2,5,6,9,10-Hexachlorodecane (CP-4) was subjected to in vitro biotransformation using human and carp liver microsomes. Five types of CP-4 metabolites (OH-, keto-, enol-, aldehyde- and carboxy-CP-4) were identified in human liver microsomer while only mono-OH-CP-4 was found in the carp liver microsomes. Kinetic studies revealed that the formation of mono-, di-, tri-hydroxylated CP-4, keto-, enol-, and aldehyde-CP-4 in human liver microsomes was best described by substrate inhibition models, whereas the formation of carboxylated CP-4 metabolites best fit the Michaelis-Menten model.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
December 2024
Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Objective: The objective of this study was to determine the apparent intrinsic clearance (Cl) and fraction unbound in human liver microsomes (f) of 86 marketed central nervous system (CNS) drugs and to predict the in vivo hepatic blood clearance (CL).
Methods: Cl in human liver microsomes (HLM) was determined by substrate depletion, and f was determined by equilibrium dialysis. The relationship between lipophilicity (logP) and unbound intrinsic clearance (Cl) was explored using the Biopharmaceutical Drug Disposition Classification System (BDDCS) and Extended Clearance Classification System (ECCS).
Basic Clin Pharmacol Toxicol
January 2025
Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
The worldwide legalization of medicinal cannabis has led to an increased use of products made by commercial operators. These products often contain minor cannabinoids such as cannabinol (CBN) which are advertised to improve sleep. Products are also available in which CBN is combined with conventional therapies, with a common product containing both CBN and the widely used sleep-aid melatonin.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China. Electronic address:
Targeting the biosynthetic pathway of mycolic acid is highly attractive to researchers in the field of novel anti-tubercular drug development. Pks13-TE is an essential catalytic component in the last assembling step of mycolic acid, and the co-crystal structures of the Pks13-TE-inhibitor complex provide insight into ligand recognition. Based on a structure-guided strategy, N-aryl indole derivatives were designed, synthesized, and evaluated for their antitubercular activities.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA; Department of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA. Electronic address:
Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits arise either from the direct inhibition of mitochondrial pyruvate metabolism or from the metabolic rewiring when pyruvate entry is inhibited. However, current MPC inhibitors are either nonspecific or possess poor pharmacokinetic properties.
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