Oral bioavailability studies of S-nitrosoglutathione using intestinal barrier models by liquid chromatography coupled with mass spectrometry after labeling with the nitrogen isotope 15 Haiyan Yu To cite this version: Haiyan Yu. Oral bioavailability studies of S-nitrosoglutathione using intestinal barrier models by liquid chromatography coupled with mass spectrometry after labeling with the nitrogen isotope 15. Biochemistry, Molecular Biology. Université de Lorraine, 2018. English. NNT : 2018LORR0100. tel-01921077 HAL Id: tel-01921077 https://hal.univ-lorraine.fr/tel-01921077 Submitted on 3 Dec 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm Ecole Doctorale BioSE (Biologie-Santé-Environnement) Thèse Présentée et soutenue publiquement pour l’obtention du titre de DOCTEUR DE l’UNIVERSITE DE LORRAINE Mention : « Sciences de la Vie et de la Santé » par Haiyan YU Etude de la biodisponibilité orale du S-nitrosoglutathion au moyen de modèles de la barrière intestinale par chromatographie en phase liquide couplée à la spectrométrie de masse après marquage par l’isotope 15 de l’azote Le 29 août 2018 Membres du jury: Rapporteurs: Emilie DESTANDAU Dr HDR, UMR 7311, Institut de Chimie Organique et Analytique, Université d'Orléans, Orléans, France Elke RICHLING Pr, Department of Food Chemistry and Toxicity, University of Kaiserslautern, Kaiserslautern, Germany Examinateurs: Pierre LEROY Pr, EA 3452, Université de Lorraine, Nancy, France (directeur de thèse) Patrick CHAIMBAULT Pr, EA 4632, Université de Lorraine, Metz, France (co-directeur de thèse) Membres invités: Igor CLAROT Pr, EA 3452, Université de Lorraine, Nancy, France Thierry OSTER Pr, UR AFPA USC INRA 340, Biochimie et Biologie Moléculaire, Université de Lorraine, Nancy, France ---------------------------------------------------------------------------------------------------------------------------- EA 3452 CITHEFOR "Cibles thérapeutiques, formulation et expertise préclinique du médicament", 5, rue Albert Lebrun, BP 80403, 54001 NANCY Cedex, France Acknowledgements When I start to write acknowledgements, I feel a little sad, because the day to say good-bye is coming. The past three years is a gift to me, I like Nancy, I like the sweet dessert coupled with bitter coffee, I like being with you. Dear Dr. Emilie Destandau (Université d'Orléans - Pôle de chimie) and Pr. Elke Richling (University of Kaiserslautern), thank you very much for agreeing to be “Rapporteurs” of my PhD thesis. Dear Pr. Igor Clarot (Université de Lorraine) and dear Pr. Thierry Oster (Université de Lorraine), thank you so much for accepting as the jury member of my work. Hope you will enjoy the day. Dear Pr. Pierre Leroy, thank you for giving me the chance to be your student, it is an honor. Many students are jealous of me, because I have you as my supervisor. Thank you for your serious working attitude and strong exutive ability. You always tell me not to depend on you too much, it is not easy because you are too reliable. Thank you for training me, inspiring me, caring me. Thank you for allowing me to act like a child and always forgiving me, I really enjoy the time with you. You are a responsible teacher, a truly friend, an interesting person. Dear Pr. Patrick Chaimbault, thank you for being my co-supervisor, the work in Metz is like a vocation, it makes me very relaxed. Thank you for trusting me, explaining and teaching me how to use LC coupled with mass spectrometry. Thank you for showing me how to balance family and work, you are a great father and patient teacher. Thank you for giving me such happy periods. Dear Pr. Philippe Maincent, thank you for creating the collaboration between falcuty of pharmacy in Wuhan University and university of Lorraine. It contributes to both science and friendship development. Thank you for inviting Chinese students to your home, you make us feel welcomed. Dear Dr. Anne Sapin, you are always so gentle, so kind, thank you for giving me advices about my mork. You make me realize that eventhough every person in the lab has her/his individual work, but we are family. Thank you for caring about my personal life. Dear Dr. Ariane Boudier, thank you for showing your principles. I remember the moment that you tell us to wear glasses when carrying out the experiments. This is for our safety. Our lab needs you. Thank you for giving us Chinese money. Dear Dr. Caroline Gaucher, thank you for your caring about me, you come to the lab on weekends to support my work relating to cells. I know you have done more but without saying anything. Thank you very much for being so nice to me. Dear Marianne Parent, thank you for staying in our lab, I like you. You work efficiently, you are easygoing, and you have inspired me that I have the potential to be a talent person in the future if I have good plans and work hard. Dear Pr. Alain Le Faou, Pr. Isabelle Lartaud, thank you for your help and suggestions in my work. Dear friends, Marie-Lynda Bouressam, Justine Bonetti, Romain Schmitt, Yi Zhou, Hui Ming, Arnaud Pallotta, Eugenia Belcastro…, thank you for accompanying me, working with me. You are my sisters and brothers in France. I miss the time we drink, eat, and chat together. Dear Isabelle Fries, Philippe Giummelly, Nathalie Degousee, Pascale Carnet, and other colleagues in EA 3452 CITHEFOR, thank you for your help in my work and my personal life. I will never forget my families in China, especially dear Zhang Liao, without your selfless love, it will be difficult for me to live abroad. I will keep on loving you for the rest of my life. It is my luck to meet you guys. I am a little shy to tell you how wonderful you are in my eyes, but I am really grateful to meet you, know you and have feelings for you. I hope you will travel in China some day in the future, and I will be exicited to be your tourist guide. I wish all of you are healthy, strong, joyfull and live happily forever. Table of contents Scientific works ........................................................................................................ 1 Publications ........................................................................................................... 1 Oral presentations ................................................................................................. 1 Poster communications ........................................................................................ 2 List of tables, figures and abbreviations ................................................................ 3 Tables ..................................................................................................................... 3 Figures ................................................................................................................... 6 Abbreviations ...................................................................................................... 13 General introduction .............................................................................................. 17 Introduction ............................................................................................................. 25 Review: “Labeling nitrogen species with the stable isotope 15N for their measurement by separative methods coupled with mass spectrometry: a review” in Talanta (191 (2018) 491–503) ............................................................ 27 1st Chapter: Development and validation of bioanalytical methods dedicated to the measurement of NO species labeled with the stable nitrogen isotope 15 .. 62 1. Experimental paper: “Comparison between two derivatization methods of nitrite ion labeled with 15N applied to liquid chromatography-tandem mass spectrometry” in Analytical Methods (10 (2018) 3830–3836) ........................... 68 2. Experimental paper: “Higher-energy Collision Dissociation for the quantification by liquid chromatography/tandem ion trap mass spectrometry of nitric oxide metabolites coming from S-nitrosoglutathione in an in vitro model of intestinal barrier” in Rapid Communications in Mass Spectrometry (under minor revision) ........................................................................................ 76 2nd Chapter: Intestinal permeability studies of S-nitrosothiols using two models ..............................................................................................................................