دورية أكاديمية
Mycolactone as Analgesic: Subcutaneous Bioavailability Parameters
| العنوان: | Mycolactone as Analgesic: Subcutaneous Bioavailability Parameters |
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| المؤلفون: | Babonneau, Jérémie, Bréard, Dimitri, Reynaert, Marie-Line, Marion, Estelle, Guilet, David, Saint André, Jean-Paul, Croue, Anne, Brodin, Priscille, Richomme, Pascal, Marsollier, Laurent |
| المساهمون: | ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), SFR UA 4207 QUAlité et SAnté du Végétal (QUASAV), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-AGROCAMPUS OUEST-Ecole supérieure d'Agricultures d'Angers (ESA), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CRLCC - Centre Paul Papin (CRLCC Paul Papin), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER-UNICANCER, This work was supported by the region Pays de la Loire (Kalmos project), the Agence Nationale de Recherche (ANR-17-CE18-0001), the Institut Pasteur of Lille (granted to PB and M-LR), the Inserm Program ATIP avenir (granted to LM), the region Pays de la Loire (Kalmos project) and Angers University., ANR-17-CE18-0001,AT2R-TRAAK-BIOANALGESICS,Caractérisations moléculaires et cellulaires de voies de signalisation de la douleur: contrôle de la douleur dans l'ulcère de buruli comme source d'inspiration pour la conception rationnelle de nouveaux analgésiques puissants(2017) |
| المصدر: | ISSN: 1663-9812 ; Frontiers in Pharmacology ; https://inserm.hal.science/inserm-02100552Test ; Frontiers in Pharmacology, 2019, 10, pp.378. ⟨10.3389/fphar.2019.00378⟩. |
| بيانات النشر: | HAL CCSD Frontiers |
| سنة النشر: | 2019 |
| المجموعة: | Université de Nantes: HAL-UNIV-NANTES |
| مصطلحات موضوعية: | biological action, Mycobacterium ulcerans, mycolactone, analgesia, bioavailability, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | Jérémie Babonneau, Dimitri Bréard and Marie-Line Reynaert have contributed equally to this work. Priscille Brodin, Pascal Richomme and Laurent Marsollier are co-senior authors. ; International audience ; Mycobacterium ulcerans is the bacillus responsible for Buruli ulcer, an infectious disease and the third most important mycobacterial disease worldwide, after tuberculosis and leprosy. M. ulcerans infection is a type of panniculitis beginning mostly with a nodule or an oedema, which can progress to large ulcerative lesions. The lesions are caused by mycolactone, the polyketide toxin of M. ulcerans. Mycolactone plays a central role for host colonization as it has immunomodulatory and analgesic effects. On one hand, mycolactone induces analgesia by targeting type-2 angiotensin II receptors (AT 2 R), causing cellular hyperpolarization and neuron desensitization. Indeed, a single subcutaneous injection of mycolactone into the mouse footpad induces a long-lasting hypoesthesia up to 48 h. It was suggested that the long-lasting hypoesthesia may result from the persistence of a significant amount of mycolactone locally following its injection, which could be probably due to its slow elimination from tissues. To verify this hypothesis, we investigated the correlation between hypoesthesia and mycolactone bioavailability directly at the tissue level. Various quantities of mycolactone were then injected in mouse tissue and hypoesthesia was recorded with nociception assays over a period of 48 h. The hypoesthesia was maximal 6 h after the injection of 4 µg mycolactone. The basal state was reached 48 h after injection, which demonstrated the absence of nerve damage. Surprisingly, mycolactone levels decreased strongly during the first hours with a reduction of 70 and 90% after 4 and 10 h, respectively. Also, mycolactone did not diffuse in neighboring skin tissue and only poorly into the bloodstream upon direct injection. Nevertheless, the remaining amount was sufficient to induce hypoesthesia during 24 h. Our results thus ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | inserm-02100552; https://inserm.hal.science/inserm-02100552Test; https://inserm.hal.science/inserm-02100552/documentTest; https://inserm.hal.science/inserm-02100552/file/MarsollierEq6-2019.pdfTest |
| DOI: | 10.3389/fphar.2019.00378 |
| الإتاحة: | https://doi.org/10.3389/fphar.2019.00378Test https://inserm.hal.science/inserm-02100552Test https://inserm.hal.science/inserm-02100552/documentTest https://inserm.hal.science/inserm-02100552/file/MarsollierEq6-2019.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.86547C1C |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fphar.2019.00378 |
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