دورية أكاديمية
Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities.
| العنوان: | Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities. |
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| المؤلفون: | Fujino C; Graduate School of Biomedical and Health Sciences, Hiroshima University., Tamura Y, Tange S, Nakajima H, Sanoh S, Watanabe Y, Uramaru N, Kojima H, Yoshinari K, Ohta S, Kitamura S |
| المصدر: | The Journal of toxicological sciences [J Toxicol Sci] 2016; Vol. 41 (5), pp. 677-91. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Doku Sayō Kenkyūkai Country of Publication: Japan NLM ID: 7805798 Publication Model: Print Cited Medium: Internet ISSN: 1880-3989 (Electronic) Linking ISSN: 03881350 NLM ISO Abbreviation: J Toxicol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Sapporo, Japan Doku Sayō Kenkyūkai |
| مواضيع طبية MeSH: | Carbaryl/*metabolism , Carbaryl/*toxicity , Cholinesterase Inhibitors/*metabolism , Cholinesterase Inhibitors/*toxicity , Liver/*metabolism , Methiocarb/*metabolism , Methiocarb/*toxicity , PPAR alpha/*agonists , Receptors, Cytoplasmic and Nuclear/*agonists , Receptors, Steroid/*agonists, Animals ; Biotransformation ; COS Cells ; Carbaryl/blood ; Chlorocebus aethiops ; Constitutive Androstane Receptor ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 CYP2C19/metabolism ; Humans ; Hydrolysis ; Male ; Methiocarb/blood ; Microsomes, Liver/metabolism ; Oxidation-Reduction ; PPAR alpha/genetics ; PPAR alpha/metabolism ; Pregnane X Receptor ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Steroid/genetics ; Receptors, Steroid/metabolism ; Transfection |
| مستخلص: | The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were examined. The effects of the metabolism of methiocarb and carbaryl on their nuclear receptor activities were also examined. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide, and a novel metabolite, methiocarb sulfone were detected. Methiocarb sulfoxide was oxidized to the sulfone by liver microsomes and reduced back to methiocarb by liver cytosol. Thus, the interconversion between methiocarb and the sulfoxide was found to be a new metabolic pathway for methiocarb by liver microsomes. The product of methiocarb hydrolysis, which is methylthio-3,5-xylenol (MX), was also oxidized to sulfoxide form by rat liver microsomes. The oxidations were catalyzed by human flavin-containing monooxygenase isoform (FMO1). CYP2C19, which is a human cytochrome P450 (CYP) isoform, catalyzed the sulfoxidations of methiocarb and MX, while CYP1A2 also exhibited oxidase activity toward MX. Methiocarb and carbaryl were not enzymatically hydrolyzed by the liver microsomes, but they were mainly hydrolyzed by plasma and albumin to MX and 1-naphthol, respectively. Both methiocarb and carbaryl exhibited PXR and PPARα agonistic activities; however, methiocarb sulfoxide and sulfone showed markedly reduced activities. In fact, when methiocarb was incubated with liver microsomes, the receptor activities were decreased. In contrast, MX and 1-naphthol showed nuclear receptor activities equivalent to those of their parent carbamates. Thus, the hydrolysis of methiocarb and carbaryl and the oxidation of methiocarb markedly modified their nuclear receptor activities. |
| المشرفين على المادة: | 0 (Cholinesterase Inhibitors) 0 (Constitutive Androstane Receptor) 0 (PPAR alpha) 0 (Pregnane X Receptor) 0 (Receptors, Cytoplasmic and Nuclear) 0 (Receptors, Steroid) EC 1.14.14.1 (CYP1A2 protein, human) EC 1.14.14.1 (CYP2C19 protein, human) EC 1.14.14.1 (Cytochrome P-450 CYP1A2) EC 1.14.14.1 (Cytochrome P-450 CYP2C19) JI9431OS31 (Methiocarb) R890C8J3N1 (Carbaryl) |
| تواريخ الأحداث: | Date Created: 20160927 Date Completed: 20170410 Latest Revision: 20211204 |
| رمز التحديث: | 20221213 |
| DOI: | 10.2131/jts.41.677 |
| PMID: | 27665777 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1880-3989 |
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| DOI: | 10.2131/jts.41.677 |