6,560 results match your criteria microsomal fraction


Evaluation of species differences in the metabolism of the selective Na1.7 inhibitor DS-1971a, a mixed substrate of cytochrome P450 and aldehyde oxidase.

Xenobiotica 2021 Sep 11;51(9):1060-1070. Epub 2021 Aug 11.

Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

Nonclinical metabolite profiling of DS-1971a, a potent selective Na1.7 inhibitor, was performed to predict human metabolites.After the oral administration of radiolabelled DS-1971a, the predominant metabolite in mouse plasma was M4, a monoxide at the pyrimidine ring, while the major metabolites with the first and second highest exposure in monkey plasma were M2, a monoxide at the cyclohexane ring, and M11, a demethylated pyrazole metabolite. Read More

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September 2021

Case Study 5: Predicting the Drug Interaction Potential for Inhibition of CYP2C8 by Montelukast.

Authors:
Ken Korzekwa

Methods Mol Biol 2021 ;2342:685-693

Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.

Predicting drug-drug interactions (DDIs) from in vitro data is made difficult by not knowing concentrations of substrate and inhibitor at the target site. For in vivo targets, this is understandable, since intracellular concentrations can differ from extracellular concentrations. More vexing is that the concentration of the drug at the target for some in vitro assays can also be unknown. Read More

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Exploration of inhibition potential of isoniazid and its metabolites towards CYP2E1 in human liver microsomes through LC-MS/MS analysis.

J Pharm Biomed Anal 2021 Sep 24;203:114223. Epub 2021 Jun 24.

Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, 160062, Punjab, India. Electronic address:

Isoniazid (INH) is the first-line anti-tubercular drug that is used both for the prophylaxis as well as the treatment of tuberculosis (TB). The patients with TB are more vulnerable to secondary infections and other health complications, hence, they are usually administered a cocktail of drugs. This increases the likelihood of drug-drug interactions (DDIs). Read More

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September 2021

Mitochondrial Biotransformation of Drugs and Other Xenobiotics.

Curr Drug Metab 2021 Jun 28. Epub 2021 Jun 28.

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040 Bornova-Izmir, Turkey.

In vivo biotransformation of exposed chemicals is one of the major factors that determine the concentration and the duration of a substance at the systemic site of effect. Given that toxicity is expressed as a function of two factors, namely dose and time, the type and intensity of the toxicity are directly dependent on the chemical transformation of the exposed parent substance. This dependency involves two different situations. Read More

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A cell-free assay implicates a role of sphingomyelin and cholesterol in STING phosphorylation.

Sci Rep 2021 Jun 7;11(1):11996. Epub 2021 Jun 7.

Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA from virus or self-DNA from mitochondria/nuclei. In response to emergence of such DNAs in the cytosol, STING translocates from the endoplasmic reticulum to the Golgi, and activates TANK-binding kinase 1 (TBK1) at the trans-Golgi network (TGN). Activated TBK1 then phosphorylates STING at Ser365, generating an interferon regulatory factor 3-docking site on STING. Read More

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assembly of nuclear envelope in tobacco cultured cells.

Nucleus 2021 Dec;12(1):82-89

Faculty of Science and Engineering, Konan University, Kobe, Japan.

The coordinated regulation of the nucelar envelope (NE) reassembly during cell division is an essential event. However, there is little information on the molecular components involved in NE assembly in plant cells. Here we developed an assay of NE assembly using tobacco BY-2 cultured cells. Read More

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December 2021

Homeostasis of the ER redox state subsequent to proteasome inhibition.

Sci Rep 2021 Apr 21;11(1):8655. Epub 2021 Apr 21.

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.

Endoplasmic reticulum (ER) maintains within, an oxidative redox state suitable for disulfide bond formation. We monitored the ER redox dynamics subsequent to proteasome inhibition using an ER redox probe ERroGFP S4. Proteasomal inhibition initially led to oxidation of the ER, but gradually the normal redox state was recovered that further led to a reductive state. Read More

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Spectrophotometric Assessment of Heme Oxygenase-1 Activity in -infected Macrophages.

Bio Protoc 2020 Apr 5;10(7):e3578. Epub 2020 Apr 5.

Department of Biochemistry, University of Calcutta, Kolkata, India.

Heme oxygenase-1 (HO-1) is a stress responsive enzyme that metabolizes heme and releases free iron, carbon monoxide (CO), and biliverdin (BV), which rapidly undergoes conversion to bilirubin (BL). Estimation of bilirubin is the basis of HO-1 assay. HO-1 activity is widely employed to determine antioxidant response of cells under different physiological stress environment. Read More

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ENZYMATIC ACTIVITY IN MICROSOMES, LIPID PEROXIDATION OF MICE HEPATOCYTES UNDER THE SODIUM FLUORIDE.

Georgian Med News 2021 Jan(310):169-176

The State Institution "Lugansk State Medical University", Rubizhne, Ukraine.

Fluorine is one of the most widespread and necessary microelements for the body of animals and humans, which is necessary in a clearly limited amount. Different concentrations of fluorine can affect the state of lipid peroxidation, as well as the functional state of the microsomes of liver hepatocytes. The studies were carried out on mature Wistar rats weighing 180-220 g. Read More

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January 2021

16-Picolyl-androsterone derivative exhibits potent 17β-HSD3 inhibitory activity, improved metabolic stability and cytotoxic effect on various cancer cells: Synthesis, homology modeling and docking studies.

J Steroid Biochem Mol Biol 2021 06 18;210:105846. Epub 2021 Feb 18.

Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU De Québec - Research Center, Québec City, Québec, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Québec, G1V 0A6, Canada. Electronic address:

A new androsterone derivative bearing a 16β-picolyl group (compound 5; FCO-586-119) was synthetized in four steps from the lead compound 1 (RM-532-105). We measured its inhibitory activity on 17β-HSD3 using microsomal fraction of rat testes as well as transfected LNCaP[17β-HSD3] cells. We then assessed its metabolic stability as well as its cytotoxic effect against a panel of cancer cell lines. Read More

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Evaluation of Tissue Binding in Three Tissues across Five Species and Prediction of Volume of Distribution from Plasma Protein and Tissue Binding with an Existing Model.

Drug Metab Dispos 2021 Apr 2;49(4):330-336. Epub 2021 Feb 2.

Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California

Volume of distribution (V) is a primary pharmacokinetic parameter used to calculate the half-life and plasma concentration-time profile of drugs. Numerous models have been relatively successful in predicting V, but the model developed by Korzekwa and Nagar is of particular interest because it utilizes plasma protein binding and microsomal binding data, both of which are readily available in vitro parameters. Here, Korzekwa and Nagar's model was validated and expanded upon using external and internal data sets. Read More

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[The development and experimental evaluation of the effectiveness of a new specialized food based on dried mare's milk during exercise].

Vopr Pitan 2020;89(6):91-103. Epub 2020 Nov 20.

Almaty Technological University, 050012, Almaty, Republic of Kazakhstan.

The development and implementation of effective means to improve performance, endurance, rapid recovery of the body after physical exertion and, ultimately, improve athletic performance are still relevant. of the work was to develop a new specialized product based on dry mare's milk, as well as to evaluate its effectiveness on an experimental model of physical activity. . Read More

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November 2020

Regulation of the microsomal proteome by salicylic acid and deficiency of phosphatidylinositol-4-kinases β1 and β2 in Arabidopsis thaliana.

Proteomics 2021 03 23;21(5):e2000223. Epub 2021 Feb 23.

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Prague, Czech Republic.

Phosphatidylinositol-4-kinases β1 and β2 (PI4Kβ1/PI4Kβ2), which are responsible for phosphorylation of phosphatidylinositol to phosphatidylinositol-4-phosphate, have important roles in plant vesicular trafficking. Moreover, PI4Kβ1/PI4Kβ2 negatively regulates biosynthesis of phytohormone salicylic acid (SA), a key player in plant immune responses. The study focused on the effect of PI4Kβ1/PI4Kβ2 deficiency and SA level on the proteome of microsomal fraction. Read More

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Parameterization of Microsomal and Cytosolic Scaling Factors: Methodological and Biological Considerations for Scalar Derivation and Validation.

Eur J Drug Metab Pharmacokinet 2021 Mar 19;46(2):173-183. Epub 2020 Dec 19.

Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.

Mathematical models that can predict the kinetics of compounds have been increasingly adopted for drug development and risk assessment. Data for these models may be generated from in vitro experimental systems containing enzymes contributing to metabolic clearance, such as subcellular tissue fractions including microsomes and cytosol. Extrapolation from these systems is facilitated by common scaling factors, known as microsomal protein per gram (MPPG) and cytosolic protein per gram (CPPG). Read More

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metabolism assessment of thiacloprid in rainbow trout and rat by LC-UV and high resolution-mass spectrometry.

Xenobiotica 2021 May 15;51(5):536-548. Epub 2021 Mar 15.

Office of Research and Development, Center for Computational Toxicology and Exposure, Great Lakes Toxicology and Ecology Division, United States Environmental Protection Agency, Duluth, MN, USA.

Thiacloprid (THI) is a widely used neonicotinoid insecticide where concerns have been raised regarding low absorption by crops, substantial distribution in surrounding areas, and potential adverse effects to terrestrial and aquatic organisms.Prior to this study, there was very limited information addressing the (precision-cut liver slices) metabolism of THI by fish species and the metabolic pathways regulating its potential for adverse effects.The and biotransformation pathway of THI is defined by the formation of three primary metabolites (TM1, TM2 and TM3) via separate paths differentiated by reductive decyanation, reductive dechlorination with hydration and dealkylation processes, respectively. Read More

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Evaluation of a Competitive Equilibrium Dialysis Approach for Assessing the Impact of Protein Binding on Clearance Predictions.

J Pharm Sci 2021 01 15;110(1):536-542. Epub 2020 Sep 15.

Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA 94080.

Fraction unbound (f) is an important consideration when characterizing the ADME properties of drug candidates. For highly bound compounds, there can be low confidence in quantifying f introducing uncertainty in certain parameter estimations. Specifically, predictions of clearance (CL) rely on accurate f values measured in plasma (f) and microsomes (f) to scale in vitro intrinsic CL to in vivo CL. Read More

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January 2021

Investigating the Theoretical Basis for In Vitro-In Vivo Extrapolation (IVIVE) in Predicting Drug Metabolic Clearance and Proposing Future Experimental Pathways.

AAPS J 2020 09 10;22(5):120. Epub 2020 Sep 10.

Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, 513 Parnassus Ave Rm HSE 1164, UCSF Box 0912, San Francisco, California, 94143, USA.

Extensive studies have been conducted to predict in vivo metabolic clearance from in vitro human liver metabolism parameters (i.e., in vitro-in vivo extrapolation (IVIVE)) with little success. Read More

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September 2020

Gender differences in plasma pharmacokinetics and hepatic metabolism of geissoschizine methyl ether from Uncaria hook in rats.

J Ethnopharmacol 2021 Jan 6;264:113354. Epub 2020 Sep 6.

Tsumura Kampo Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan. Electronic address:

Ethnopharmacological Relevance: Geissoschizine methyl ether (GM), an indole alkaloid from Uncaria hook, is an active ingredient in the traditional Japanese Kampo medicine yokukansan, which is used to treat neurosis, insomnia, irritability, and night crying in children.

Aim Of The Study: Recent our pharmacokinetic studies suggested that there may be gender differences in the plasma concentrations of GM in rats, but not in humans. However, the details of this difference remain unverified. Read More

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January 2021

In vivo ESR imaging of redox status in mice after X-ray irradiation, measured by acyl-protected hydroxylamine probe, ACP.

Free Radic Biol Med 2020 11 4;160:596-603. Epub 2020 Sep 4.

National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan; Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan. Electronic address:

More detailed investigations on the in vivo redox status are needed to elucidate the mechanisms contributing to damage caused by ionizing radiation. In the present study, the in vivo redox status of mice was examined using in vivo electron spin resonance (ESR) imaging after an intraperitoneal injection of 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP) as a probe. ACP is easily hydrolyzed to its hydroxylamine form in the mouse body, and the interconversion between hydroxylamine and the corresponding nitroxyl radical reflects the biological redox status. Read More

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November 2020

Elucidating pesticide sensitivity of two endogeic earthworm species through the interplay between esterases and glutathione S-transferases.

Chemosphere 2021 Jan 18;262:127724. Epub 2020 Jul 18.

Univ Avignon, Aix Marseille Univ, CNRS, IRD, IMBE, Pôle Agrosciences, 301 Rue Baruch de Spinoza, BP 21239, 84916, Avignon, France. Electronic address:

Earthworms are common organisms in soil toxicity-testing framework, and endogeic species are currently recommended due to their ecological role in agroecosystem. However, little is known on their pesticide metabolic capacities. We firstly compared the baseline activity of B-esterases and glutathione-S-transferase in Allolobophora chlorotica and Aporrectodea caliginosa. Read More

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January 2021

Hepatic Synaptotagmin 1 is involved in the remodelling of liver plasma- membrane lipid composition and gene expression in male Apoe-deficient mice consuming a Western diet.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 12 7;1865(12):158790. Epub 2020 Aug 7.

Departamento Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IISA), Universidad de Zaragoza, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain; Instituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, Spain. Electronic address:

Background And Aims: The molecular mechanisms by which the liver develops steatotic disease still remain unclear. Previous studies using nutritional and genetic models of hepatic steatosis in mice showed that liver synaptotagmin 1 (Syt1) expression was associated with lipid droplet area. Hepatic Syt1 overexpression was used as a tool to explore its effect on hepatic and plasma lipids. Read More

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December 2020

Etomidate is devoid of genotoxicty and mutagenicity in human lymphocytes and in the Salmonella typhimurium/microsomal activation test.

Toxicol In Vitro 2020 Oct 15;68:104946. Epub 2020 Jul 15.

Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.

No carcinogenesis or mutagenesis studies have been carried out with etomidate. The current study showed that etomidate has weak cytotoxic potential after 48 h exposure in human lymphocytes and has no hemolytic activity. The weak cytotoxicity seems to be related with redox imbalance of etomidate (40. Read More

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October 2020

Predicting the Potential for Cannabinoids to Precipitate Pharmacokinetic Drug Interactions via Reversible Inhibition or Inactivation of Major Cytochromes P450.

Drug Metab Dispos 2020 10 25;48(10):1008-1017. Epub 2020 Jun 25.

Department of Pharmaceutics, University of Washington, Seattle, Washington (S.B., N.M., J.D.U.); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (M.F.P.); and Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (M.F.P., J.D.U.)

Cannabis is used for both recreational and medicinal purposes. The most abundant constituents are the cannabinoids - cannabidiol (CBD, nonpsychoactive) and (-)--Δ-tetrahydrocannabinol (THC, psychoactive). Both have been reported to reversibly inhibit or inactivate cytochrome P450 (CYPs) enzymes. Read More

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October 2020

Biomarker considerations in monitoring petrogenic pollution using the mussel Mytilus galloprovincialis.

Environ Sci Pollut Res Int 2020 Sep 5;27(25):31854-31862. Epub 2020 Jun 5.

Laboratorio de Fisiología y Genética Marina (FIGEMA), Centro de Estudios Avanzados en Zonas Áridas, Universidad Católica del Norte, Larrondo 1281, Coquimbo, Chile.

Mussels are worldwide bioindicators in pollution monitoring since they fulfil the requirements for being good sentinels. However, some methodological concerns arise in the use of particular biomarkers, particularly those displaying low enzymatic rates and/or limited responsiveness to chemicals and biological-related variability. In the present study, the suitability of oxidative stress and detoxification parameters when using mussels as sentinels of polycyclic aromatic hydrocarbon (PAH) pollution is addressed. Read More

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September 2020

Direct Comparison of Total Clearance Prediction: Computational Machine Learning Model versus Bottom-Up Approach Using In Vitro Assay.

Mol Pharm 2020 07 12;17(7):2299-2309. Epub 2020 Jun 12.

Global DMPK, Takeda California Inc., San Diego, California 92121, United States.

The in vitro-in vivo extrapolation (IVIVE) approach for predicting total plasma clearance (CL) has been widely used to rank order compounds early in discovery. More recently, a computational machine learning approach utilizing physicochemical descriptors and fingerprints calculated from chemical structure information has emerged, enabling virtual predictions even earlier in discovery. Previously, this approach focused more on in vitro intrinsic clearance (CL) prediction. Read More

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The Curcumin Derivative, H10, Suppresses Hormone-Dependent Prostate Cancer by Inhibiting 17β-Hydroxysteroid Dehydrogenase Type 3.

Front Pharmacol 2020 8;11:637. Epub 2020 May 8.

Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China.

The 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) enzyme is a potential therapeutic target for hormone-dependent prostate cancer, as it is the key enzyme in the last step of testosterone (T) biosynthesis. A curcumin analog, H10, was optimized for inhibiting T production in LC540 cells that stably overexpressed 17β-HSD3 enzyme (LC540 [17β-HSD3]) (P < 0.01), without affecting progesterone (P) synthesis. Read More

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Seasonal variability of chemical composition and mutagenic effect of organic PM2.5 pollutants collected in the urban area of Wrocław (Poland).

Sci Total Environ 2020 Sep 27;733:138911. Epub 2020 Apr 27.

Faculty of Environmental Engineering, Wrocław University of Science and Technology, Wybrzeże S. Wyspiańskiego 27, 50-370 Wrocław, Poland. Electronic address:

The objective of the study was the assessment of the mutagenicity of chemical pollutants adsorbed on suspended particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) in the four seasons. Read More

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September 2020

Biochemical Characterization and Allosteric Modulation by Magnesium of (Na, K)-ATPase Activity in the Gills of the Red Mangrove Crab Goniopsis cruentata (Brachyura, Grapsidae).

J Membr Biol 2020 06 22;253(3):229-245. Epub 2020 May 22.

Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP, 14040-901, Brazil.

We provide a kinetic characterization of (Na, K)-ATPase activity in a posterior gill microsomal fraction from the grapsid crab Goniopsis cruentata. (Na, K)-ATPase activity constitutes 95% of total ATPase activity, and sucrose density centrifugation reveals an ATPase activity peak between 25 and 35% sucrose, distributed into two, partially separated protein fractions. The (Na, K)-ATPase α-subunit is localized throughout the ionocyte cytoplasm and has an M of ≈ 10 kDa and hydrolyzes ATP obeying cooperative kinetics. Read More

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Comparative liver metabolic enzyme activity of cytochrome P450 and glutathione-S-transferase in crocodile (Crocodylus siamensis) and livestock.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Sep 5;235:108784. Epub 2020 May 5.

Diagnostic Center for Animal Health Unit, Faculty of Veterinary Medicine, Kasetsart University Kamphaeng Saen Campus, Nakhon Pathom 73140, Thailand. Electronic address:

This study aimed to compare the metabolism of detoxification liver enzymes activity of CYP1A2, CYP2E1, the GST enzymes activity for class pi, mu, alfa, and the universal GST between crocodile and livestock, plus the relationship of these two enzyme activities in the crocodile. Interestingly, the CYP1A2 and CYP2E1 were existent in the freshwater crocodile livers microsomal enzyme activities, and these two enzymes could be determined in both pig and chicken. Also, the universal GST, alpha, mu, and pi class of phase II were presented in the crocodile liver cytosolic fractions, and these three enzymes could also be found in pig and chicken. Read More

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September 2020

Affinity Labeling and Purification of Plant Chitin-Binding LysM Receptor with Chitin Octasaccharide Derivatives.

Methods Mol Biol 2020 ;2132:401-412

Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.

Lysin motif (LysM) is a carbohydrate-binding modules found in all kingdoms. LysM binds to N-acetylglucosamine-containing molecules such as peptidoglycan, chitin, Nod factor, and Myc factor and is found in peptidoglycan hydrolases, chitinases, and plant pathogen effectors and plant receptor/co-receptor for defense and symbiosis signaling. This chapter describes the synthesis of a nonradioactive chitin ligand, biotinylated chitin octasaccharide, (GlcNAc)-Bio, and its application for the detection and characterization of chitin-binding LysM receptor CEBiP in the microsomal membrane fraction of rice suspension-cultured cells by affinity labeling. Read More

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