Background: Oxidative stress produced by reactive oxygen species (ROS) has been linked to the development of several diseases such as cardiovascular, cancer, and neurodegenerative diseases. This study investigates the possible protective effect of extra virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) on oxidative stress and fatty acid profile of erythrocytes in 2,4-D treated rats.
Methods: Male Wistar rats were divided randomly into eight groups: control (C), (2,4-D) at a dose of 5 mg/kg b.w., (2,4-D/EVOO) was given 2,4-D plus EVOO, (2,4-D/OOHF) that received 2,4-D plus hydrophilic fraction, (2,4-D/OOLF) treated with 2,4-D plus lipophilic fraction, (EVOO) that received only EVOO, (OOHF) was given hydrophilic fraction and (OOLF) treated with lipophilic fraction. These components were daily administered by gavages for 4 weeks.
Results: 2,4-D treatment lead to decrease of antioxidant enzyme activities, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) associated with a higher amount of MDA level. Erythrocyte membranes' fatty acid composition was also significantly modified with 2,4-D exposure. EVOO and hydrophilic fraction supplemented to rats with or not 2,4-D treatment enhanced the antioxidant enzyme activities and reduced the MDA level. However, lipophilic fraction did not show any improvement in oxidative damage induced by 2,4-D in spite its richness in MUFA and vitamins.
Conclusion: EVOO administered to 2,4-D-treated rats protected erythrocyte membranes against oxidative damage by means of preventing excessive lipid peroxidation to increase the MUFA composition and increase maintaining antioxidants enzymes at normal concentrations.
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http://dx.doi.org/10.1186/1476-511X-9-89 | DOI Listing |
Eur 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).
J Med Chem
December 2024
Oncology Medicinal Chemistry Worldwide Research and Development, Pfizer, Inc., 10770 Science Center Drive, La Jolla, California 92121, United States.
Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Tianjin Key Laboratory of Intelligent Breeding of Major Crops, Tianjin 300392, China; Tianjin Agricultural University, Tianjin 300392, China. Electronic address:
Sanxan has important application value in the field of bioactive substance delivery. However, the current sanxan emulsion gel method has certain limitations in delivering heat-sensitive lipophilic bioactive substances. In this study, the acid-gelling properties of sanxan were utilized to prepare sanxan emulsion gel microcapsules (SEGMs) by extrusion dripping method.
View Article and Find Full Text PDFAnal Chim Acta
January 2025
Department of Toxicology and Health Inspection and Quarantine, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, 300070, China. Electronic address:
Background: In recent years, the increasing accumulation of estrogen pollutants in the environment has raised concerns about their impact on human health, necessitating the development of highly sensitive detection methods for trace pollutant enrichment and analysis in environmental samples. Online pretreatment detection technology offers significant advantages over conventional offline techniques, including high automation, minimal human intervention, and improved efficiency. However, the key to successful implementation lies in the advancement of novel adsorbent materials.
View Article and Find Full Text PDFAnal Chim Acta
January 2025
HAB Monitoring & Reference Branch, Stressor Detection and Impacts Division, National Centers for Coastal Ocean Science, NOAA National Ocean Service, 331 Fort Johnson Road, Charleston, SC, 29412, USA.
Background: Microcystins (MCs) and nodularins (NODs) produced by cyanobacteria occur in ambient freshwaters and across the freshwater-marine continuum, and pose health threats through drinking and recreational waters, as well as food resources. Approximately 300 MC and NOD toxins have been published, but less than 15 of them are commercially available as toxin standards. Our aim herein was to rapidly identify and quantify all toxin congeners, including those without standards, in water samples even at low abundance by reversed-phase solid phase extraction (SPE)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) to provide insights into toxin levels and potential toxicity.
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