RT Journal Article SR Electronic T1 Drug-Metabolizing and Antioxidant Enzymes in Monosodium L-Glutamate Obese Mice JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 258 OP 265 DO 10.1124/dmd.114.061176 VO 43 IS 2 A1 Petra Matoušková A1 Hana Bártíková A1 Iva Boušová A1 Lucie Levorová A1 Barbora Szotáková A1 Lenka Skálová YR 2015 UL http://dmd.aspetjournals.org/content/43/2/258.abstract AB 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.