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Research ArticleArticle

Drug-Metabolizing and Antioxidant Enzymes in Monosodium L-Glutamate Obese Mice

Petra Matoušková, Hana Bártíková, Iva Boušová, Lucie Levorová, Barbora Szotáková and Lenka Skálová
Drug Metabolism and Disposition February 2015, 43 (2) 258-265; DOI: https://doi.org/10.1124/dmd.114.061176
Petra Matoušková
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Hana Bártíková
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Iva Boušová
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Lucie Levorová
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Barbora Szotáková
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Lenka Skálová
Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic
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Abstract

The prevalence of obesity is rapidly increasing across the world. Physiologic alterations associated with obesity are known to alter enzyme expression and/or activities. As drug-metabolizing and antioxidant enzymes serve as defense system against potentially toxic compounds, their modulation might have serious consequences. In this work, we studied selected antioxidant and drug-metabolizing enzymes (DME) in monosodium glutamate–mouse model of obesity. Specific activities, protein, and mRNA expressions of these enzymes in liver as well as in small intestine were compared in obese male mice and in their lean counterparts. Furthermore, expression of the NF-E2–related factor 2 (Nrf2) and its relation to obesity were tested. Obtained results showed that obesity affects expression and/or activities of some DME and antioxidant enzymes. In obese mice, upregulation of UDP-glucuronosyltransferases 1A (UGT1A), NAD(P)H:quinone oxidoreductase 1 (NQO1), nuclear transcription factor Nrf2, and downregulation of some isoforms of glutathione S-transferases (GST) were observed. Most of these changes were tissue and/or isoform specific. NQO1 seems to be regulated transcriptionally via Nrf2, but other enzymes might be regulated post-transcriptionally and/or post-translationally. Enhanced expression of Nrf2 in livers of obese mice is expected to play a role in protective adaptation. In contrast, elevated activities of NQO1 and UGT1A may cause alterations in drug pharmacokinetics in obese individuals. Moreover, decreased capacity of GST in obese animals indicates potentially reduced antioxidant defense and weaker chemoprotection.

Footnotes

    • Received September 17, 2014.
    • Accepted December 3, 2014.
  • This work was supported by the Czech Science Foundation [Centre of Excellence, Grant P303/12/G163] and by the European Social Fund and the state budget of the Czech Republic [Project CZ.1.07/2.3.00/30.0022].

  • dx.doi.org/10.1124/dmd.114.061176.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 43 (2)
Drug Metabolism and Disposition
Vol. 43, Issue 2
1 Feb 2015
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Research ArticleArticle

Drug-Metabolizing and Antioxidant Enzymes in Obese Mice

Petra Matoušková, Hana Bártíková, Iva Boušová, Lucie Levorová, Barbora Szotáková and Lenka Skálová
Drug Metabolism and Disposition February 1, 2015, 43 (2) 258-265; DOI: https://doi.org/10.1124/dmd.114.061176

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Research ArticleArticle

Drug-Metabolizing and Antioxidant Enzymes in Obese Mice

Petra Matoušková, Hana Bártíková, Iva Boušová, Lucie Levorová, Barbora Szotáková and Lenka Skálová
Drug Metabolism and Disposition February 1, 2015, 43 (2) 258-265; DOI: https://doi.org/10.1124/dmd.114.061176
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