“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats
4-Hydroxynonenal (HNE) is a cytotoxic and genotoxic lipid oxidation secondary product which is formed endogenously upon peroxidation of cellular n-6 fatty acids. However, it can also be formed in food or during digestion, upon peroxidation of dietary lipids. Several studies have evidenced that we ar...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231714001402 |
| _version_ | 1818361981281763328 |
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| author | Julia Keller Maryse Baradat Isabelle Jouanin Laurent Debrauwer Françoise Guéraud |
| author_facet | Julia Keller Maryse Baradat Isabelle Jouanin Laurent Debrauwer Françoise Guéraud |
| author_sort | Julia Keller |
| collection | DOAJ |
| description | 4-Hydroxynonenal (HNE) is a cytotoxic and genotoxic lipid oxidation secondary product which is formed endogenously upon peroxidation of cellular n-6 fatty acids.
However, it can also be formed in food or during digestion, upon peroxidation of dietary lipids. Several studies have evidenced that we are exposed through food to significant concentrations of HNE that could pose a toxicological concern. It is then of importance to known how HNE is metabolized after oral administration. Although its metabolism has been studied after intravenous administration in order to mimick endogenous formation, its in vivo fate after oral administration had never been studied.
In order to identify and quantify urinary HNE metabolites after oral administration in rats, radioactive and stable isotopes of HNE were used and urine was analyzed by radio-chromatography (radio-HPLC) and chromatography coupled with High Resolution Mass Spectrometry (HPLC–HRMS).
Radioactivity distribution revealed that 48% of the administered radioactivity was excreted into urine and 15% into feces after 24 h, while 3% were measured in intestinal contents and 2% in major organs, mostly in the liver. Urinary radio-HPLC profiles revealed 22 major peaks accounting for 88% of the urinary radioactivity. For identification purpose, HNE and its stable isotope [1,2-13C]-HNE were given at equimolar dose to be able to univocally identify HNE metabolites by tracking twin peaks on HPLC–HRMS spectra. The major peak was identified as 9-hydroxy-nonenoic acid (27% of the urinary radioactivity) followed by classical HNE mercapturic acid derivatives (the mercapturic acid conjugate of di-hydroxynonane (DHN-MA), the mercapturic acid conjugate of 4-hydroxynonenoic acid (HNA-MA) in its opened and lactone form) and by metabolites that are oxidized in the terminal position. New urinary metabolites as thiomethyl and glucuronide conjugates were also evidenced. Some analyses were also performed on feces and gastro-intestinal contents, revealing the presence of tritiated water that could originate from beta-oxidation reactions. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-13T21:25:19Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-c5d8f4d826f04eccb86a94515b28bfaf2022-12-21T23:30:59ZengElsevierRedox Biology2213-23172015-04-014C13614810.1016/j.redox.2014.12.016“Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in ratsJulia Keller0Maryse Baradat1Isabelle Jouanin2Laurent Debrauwer3Françoise Guéraud4UMR 1331 Toxalim, INRA, INP, UPS, Team 9 “Prevention, Promotion of Carcinogenesis by Food”, BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse CEDEX, FranceUMR 1331 Toxalim, INRA, INP, UPS, Team 9 “Prevention, Promotion of Carcinogenesis by Food”, BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse CEDEX, FranceUMR 1331 Toxalim, INRA, INP, UPS, Axiom Platform, BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse CEDEX, FranceUMR 1331 Toxalim, INRA, INP, UPS, Axiom Platform, BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse CEDEX, FranceUMR 1331 Toxalim, INRA, INP, UPS, Team 9 “Prevention, Promotion of Carcinogenesis by Food”, BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse CEDEX, France4-Hydroxynonenal (HNE) is a cytotoxic and genotoxic lipid oxidation secondary product which is formed endogenously upon peroxidation of cellular n-6 fatty acids. However, it can also be formed in food or during digestion, upon peroxidation of dietary lipids. Several studies have evidenced that we are exposed through food to significant concentrations of HNE that could pose a toxicological concern. It is then of importance to known how HNE is metabolized after oral administration. Although its metabolism has been studied after intravenous administration in order to mimick endogenous formation, its in vivo fate after oral administration had never been studied. In order to identify and quantify urinary HNE metabolites after oral administration in rats, radioactive and stable isotopes of HNE were used and urine was analyzed by radio-chromatography (radio-HPLC) and chromatography coupled with High Resolution Mass Spectrometry (HPLC–HRMS). Radioactivity distribution revealed that 48% of the administered radioactivity was excreted into urine and 15% into feces after 24 h, while 3% were measured in intestinal contents and 2% in major organs, mostly in the liver. Urinary radio-HPLC profiles revealed 22 major peaks accounting for 88% of the urinary radioactivity. For identification purpose, HNE and its stable isotope [1,2-13C]-HNE were given at equimolar dose to be able to univocally identify HNE metabolites by tracking twin peaks on HPLC–HRMS spectra. The major peak was identified as 9-hydroxy-nonenoic acid (27% of the urinary radioactivity) followed by classical HNE mercapturic acid derivatives (the mercapturic acid conjugate of di-hydroxynonane (DHN-MA), the mercapturic acid conjugate of 4-hydroxynonenoic acid (HNA-MA) in its opened and lactone form) and by metabolites that are oxidized in the terminal position. New urinary metabolites as thiomethyl and glucuronide conjugates were also evidenced. Some analyses were also performed on feces and gastro-intestinal contents, revealing the presence of tritiated water that could originate from beta-oxidation reactions.http://www.sciencedirect.com/science/article/pii/S22132317140014024-HydroxynonenalLipoperoxidationMetabolismHRMSIsotope tracking |
| spellingShingle | Julia Keller Maryse Baradat Isabelle Jouanin Laurent Debrauwer Françoise Guéraud “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats Redox Biology 4-Hydroxynonenal Lipoperoxidation Metabolism HRMS Isotope tracking |
| title | “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats |
| title_full | “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats |
| title_fullStr | “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats |
| title_full_unstemmed | “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats |
| title_short | “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats |
| title_sort | twin peaks searching for 4 hydroxynonenal urinary metabolites after oral administration in rats |
| topic | 4-Hydroxynonenal Lipoperoxidation Metabolism HRMS Isotope tracking |
| url | http://www.sciencedirect.com/science/article/pii/S2213231714001402 |
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