CYP2C9 Genotype-Dependent Warfarin Pharmacokinetics: Impact of CYP2C9 Genotype on R- and S-Warfarin and Their Oxidative Metabolites

2016 ◽  
Vol 57 (3) ◽  
pp. 382-393 ◽  
Author(s):  
Darcy R. Flora ◽  
Allan E. Rettie ◽  
Richard C. Brundage ◽  
Timothy S. Tracy
Keyword(s):  
Cyp2c9 Genotype ◽  
Oxidative Metabolites

scholarly journals Impact of genetic and non-genetic factors on hepatic CYP2C9 expression and activity in Hungarian subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ferenc Fekete ◽  
Katalin Mangó ◽  
Máté Déri ◽  
Evelyn Incze ◽  
Annamária Minus ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Accurate Estimation ◽  
Mrna Levels ◽  
Cytochrome P450 Enzymes ◽  
Acid Therapy ◽  
Cyp2c9 Genotype ◽  
Amoxicillin Clavulanic Acid ◽  
Inflammatory Drugs ◽  
The Impact ◽  
Cyp2c9 Activity

AbstractCYP2C9, one of the most abundant hepatic cytochrome P450 enzymes, is involved in metabolism of 15–20% of clinically important drugs (warfarin, sulfonylureas, phenytoin, non-steroid anti-inflammatory drugs). To avoid adverse events and/or impaired drug-response, CYP2C9 pharmacogenetic testing is recommended. The impact of CYP2C9 polymorphic alleles (CYP2C9*2, CYP2C9*3) and phenoconverting non-genetic factors on CYP2C9 function and expression was investigated in liver tissues from Caucasian subjects (N = 164). The presence of CYP2C9*3 allele was associated with CYP2C9 functional impairment, and CYP2C9*2 influenced tolbutamide 4′-hydroxylase activity only in subjects with two polymorphic alleles, whereas the contribution of CYP2C8*3 was not confirmed. In addition to CYP2C9 genetic polymorphisms, non-genetic factors (co-medication with CYP2C9-specific inhibitors/inducers and non-specific factors including amoxicillin + clavulanic acid therapy or chronic alcohol consumption) contributed to the prediction of hepatic CYP2C9 activity; however, a CYP2C9 genotype–phenotype mismatch still existed in 32.6% of the subjects. Substantial variability in CYP2C9 mRNA levels, irrespective of CYP2C9 genotype, was demonstrated; however, CYP2C9 induction and non-specific non-genetic factors potentially resulting in liver injury appeared to modify CYP2C9 expression. In conclusion, complex implementation of CYP2C9 genotype and non-genetic factors for the most accurate estimation of hepatic CYP2C9 activity may improve efficiency and safety of medication with CYP2C9 substrate drugs in clinical practice.

scholarly journals STRUCTURAL ELUCIDATION OF HUMAN OXIDATIVE METABOLITES OF MURAGLITAZAR: USE OF MICROBIAL BIOREACTORS IN THE BIOSYNTHESIS OF METABOLITE STANDARDS

2005 ◽  
Vol 34 (2) ◽  
pp. 267-280 ◽  
Author(s):  
Donglu Zhang ◽  
Haiying Zhang ◽  
Nelly Aranibar ◽  
Ronald Hanson ◽  
Yande Huang ◽  
...  
Keyword(s):  
Structural Elucidation ◽  
Oxidative Metabolites

Novel oxidative metabolites of the mycoestrogen zearalenonein vitro

2007 ◽  
Vol 51 (7) ◽  
pp. 867-871 ◽  
Author(s):  
Erika Pfeiffer ◽  
Anja Heyting ◽  
Manfred Metzler
Keyword(s):  
Oxidative Metabolites

In-Vitro Toxicological and Proteomic Analysis of Furan Fatty Acids Which are Oxidative Metabolites of Conjugated Linoleic Acids

Lipids ◽  
2012 ◽  
Vol 47 (11) ◽  
pp. 1085-1097 ◽  
Author(s):  
Imme Lengler ◽  
Thorsten Buhrke ◽  
Eileen Scharmach ◽  
Alfonso Lampen
Keyword(s):  
Fatty Acids ◽  
Proteomic Analysis ◽  
Conjugated Linoleic Acids ◽  
Furan Fatty Acids ◽  
Oxidative Metabolites

scholarly journals Biochemical and Immunological implications of Lutein and Zeaxanthin

2021 ◽  
Vol 22 (20) ◽  
pp. 10910
Author(s):  
Javaria Zafar ◽  
Amna Aqeel ◽  
Fatima Iftikhar Shah ◽  
Naureen Ehsan ◽  
Umar Farooq Gohar ◽  
...  
Keyword(s):  
Food Industry ◽  
Gene Editing ◽  
Antioxidant Activities ◽  
Oxidative Degradation ◽  
Global Market ◽  
Bioactive Molecules ◽  
Attractive Alternative ◽  
Extraction And Purification ◽  
Oxidative Metabolites ◽  
Significant Attention

Throughout history, nature has been acknowledged for being a primordial source of various bioactive molecules in which human macular carotenoids are gaining significant attention. Among 750 natural carotenoids, lutein, zeaxanthin and their oxidative metabolites are selectively accumulated in the macular region of living beings. Due to their vast applications in food, feed, pharmaceutical and nutraceuticals industries, the global market of lutein and zeaxanthin is continuously expanding but chemical synthesis, extraction and purification of these compounds from their natural repertoire e.g., plants, is somewhat costly and technically challenging. In this regard microbial as well as microalgal carotenoids are considered as an attractive alternative to aforementioned challenges. Through the techniques of genetic engineering and gene-editing tools like CRISPR/Cas9, the overproduction of lutein and zeaxanthin in microorganisms can be achieved but the commercial scale applications of such procedures needs to be done. Moreover, these carotenoids are highly unstable and susceptible to thermal and oxidative degradation. Therefore, esterification of these xanthophylls and microencapsulation with appropriate wall materials can increase their shelf-life and enhance their application in food industry. With their potent antioxidant activities, these carotenoids are emerging as molecules of vital importance in chronic degenerative, malignancies and antiviral diseases. Therefore, more research needs to be done to further expand the applications of lutein and zeaxanthin.

scholarly journals Combination of LC-MS2 and GC-MS as a Tool to Differentiate Oxidative Metabolites of Zearalenone with Different Chemical Structures

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Andreas A. Hildebrand ◽  
Erika Pfeiffer ◽  
Georg Damm ◽  
Manfred Metzler
Keyword(s):  
Mass Spectra ◽  
Ion Trap ◽  
Hydrolysis Product ◽  
Chemical Structures ◽  
Ion Trap Mass Spectrometer ◽  
Fragment Ions ◽  
Oxidative Metabolites ◽  
Electron Impact Mass ◽  
Negative Electrospray Ionization ◽  
Impact Mass

Recent studies on the mammalian and fungal metabolism of the mycotoxin zearalenone (ZEN) have disclosed the formation of six regioisomers of monohydroxy-ZEN and its reductive metabolite zearalenol (ZEL). Hydroxylation occurs at the aromatic ring or at one of four positions of the aliphatic macrocycle. In addition, an aliphatic ZEN epoxide, its hydrolysis product, and other products were identified in fungal cultures. In this paper, we report the product ion spectra of the [M-H]− ions of 22 oxidative metabolites of ZEN and ZEL, obtained by LC-MS2 analysis using a linear ion trap mass spectrometer with negative electrospray ionization. The MS2 spectra exhibit qualitative and quantitative differences which allow a clear distinction of most metabolites. Moreover, GC-MS analysis of the trimethylsilylated metabolites yields electron impact mass spectra with numerous fragment ions which can be used as fingerprint to confirm the chemical structure derived by LC-MS2 analysis.

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