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1. Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

Author

Blandin, Alexia, Amosse, Jérémy, Froger, Josy, Hilairet, Grégory, Durcin, Maëva, Fizanne, Lionel, Ghesquière, Valentine, Prieur, Xavier, Chaigneau, Julien, Vergori, Luisa, Dray, Cédric, Pradère, Jean-Philippe, Blandin, Stéphanie, Dupont, Joëlle, Ducluzeau, Pierre-Henri, Dubois, Séverine, Boursier, Jérôme, Cariou, Bertrand, and Le Lay, Soazig

Published
2023
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2. Preventive effects of a nutraceutical mixture of berberine, citrus and apple extracts on metabolic disturbances in Zucker fatty rats.

Author

Siliman Misha, Mohamed, Destrumelle, Sandrine, Le Jan, Dylan, Mansour, Nahla M., Fizanne, Lionel, Ouguerram, Khadija, Desfontis, Jean-Claude, and Mallem, Mohamed-Yassine

Subjects
LABORATORY rats, METABOLIC disorders, ALKALOIDS, BERBERINE, WEIGHT loss, WEIGHT gain, SHORT-chain fatty acids, ORANGES, APPLES
Abstract

Background: The prevention of obesity represents a major health and socio-economic challenge. Nutraceuticals are regularly highlighted for their beneficial effects in preventing the metabolic disturbances associated with obesity. However, few studies have described the combined action of nutraceutical mixtures combining polyphenols with alkaloids. Objective: The aim of this study was to evaluate the effects of long-term dietary supplementation with a mixture of Berberine, Citrus and Apple extracts (BCA) in the primary prevention of obesity and its metabolic and vascular complications in the obese Zucker rat, a spontaneous model of genetic obesity and insulin resistance. Methods: Sixteen 8-week-old obese Zucker male rats were randomly divided into two groups: all rats received oral gavage daily either with water, untreated obese (U-ObZ) or BCA (BCA-ObZ) mixture for thirteen weeks. Morphological and metabolic parameters were measured along the study. Cumulative concentration-response curves to insulin, acetylcholine and phenylephrine were determined on isolated thoracic aorta. Colon permeability measurements were performed using the Ussing chamber technique. Fecal samples collected at the beginning and the end of the protocol were used as a template for amplification of the V3-V4 region of the 16S rDNA genes. Results: BCA supplementation reduced weight gain (p<0.05) and food intake (p<0.05) in the BCA-ObZ group rats compared to the U-ObZ group rats. It also improved glucose tolerance (p<0.001) and decreased fasting insulin and Homeostasis model assessment index (p<0.05). Through ex vivo experiments, the BCA mixture enhanced significantly aortic insulin relaxation (p<0.01), reduced α1-adrenoceptor-mediated vasoconstriction (p<0.01), and decreased distal colon permeability. Moreover, short-chain fatty acid producers such as Bacteroides, Blautia, and Akkermansia were found to be increased by the BCA mixture supplementation. Conclusion: The results showed that a 13-week-supplementation with BCA mixture prevented weight gain and improved glucose metabolism in obese Zucker rats. We also demonstrated that BCA supplementation improved vascular function, colonic barrier permeability and gut microbiota profile. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Lipidomic analysis of adipose-derived extracellular vesicles reveals specific EV lipid sorting informative of the obesity metabolic state

Author

Blandin, Alexia, primary, Dugail, Isabelle, additional, Hilairet, Grégory, additional, Ponnaiah, Maharajah, additional, Ghesquière, Valentine, additional, Froger, Josy, additional, Ducheix, Simon, additional, Fizanne, Lionel, additional, Boursier, Jérôme, additional, Cariou, Bertrand, additional, Lhomme, Marie, additional, and Le Lay, Soazig, additional

Published
2023
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5. Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases

Author

Fizanne, Lionel, primary, Villard, Alexandre, additional, Benabbou, Nadia, additional, Recoquillon, Sylvain, additional, Soleti, Raffaella, additional, Delage, Erwan, additional, Wertheimer, Mireille, additional, Vidal‐Gómez, Xavier, additional, Oullier, Thibauld, additional, Chaffron, Samuel, additional, Martínez, M. Carmen, additional, Neunlist, Michel, additional, Boursier, Jérôme, additional, and Andriantsitohaina, Ramaroson, additional

Published
2023
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8. Cross-linkage between bacterial taxonomy and gene functions: a study of metagenome-assembled genomes of Gut Microbiota in adult non-alcoholic fatty liver disease

Author

Canivet, Clemence, David, Norma, Pailhoriès, Helene, Briand, Martial, Guy, Cynthia, Bouchez, Olivier, Hunault, Gilles, Fizanne, Lionel, Lannes, Adrien, Oberti, Frederic, Fouchard, Isabelle, Calès, Paul, Diehl, Anna Mae, Barret, Matthieu, Boursier, Jerome, Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Duke University Medical Center, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Angers University Hospital, Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université Toulouse III - Paul Sabatier (UT3)

Subjects
nutritional and metabolic diseases, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, digestive system, digestive system diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background The reconstruction of metagenome-assembled genomes (MAGs) has emerged as a powerful approach for combining the taxonomic and functional content of microbial populations.Aim To use this new approach to highlight mechanisms linking gut microbiota to NAFLD severityMethods Stool samples were collected from 96 NAFLD patients on the day of liver biopsy. Shotgun DNA sequencing of the gut microbiota was performed on an Illumina HiSeq3000 system. Contigs were binned into MAGs according to their co-abundances and tetranucleotide frequencies using Metabat v.0.32.4. Predicted protein-coding genes were clustered in orthologous groups (OGs) with DIAMOND against the EggNOG v4.5 database. Liver biopsies were read in accordance with the NASH CRN classification.Results Fifty-four patients had NASH and 44 had significant fibrosis (F >= 2). Sequencing of DNA extracted from stools resulted in 13.8 + 3.2 million paired-end reads per sample. Of the 4,000 reconstructed MAGs, 220 in NASH patients, 192 in non-NASH patients, 203 in F >= 2 patients and 230 in F0-1 patients had > 70% completeness and < 5% contamination. Within these MAGs, 28 OGs were associated with NASH, 33 with significant fibrosis, and seven with both NASH and significant fibrosis. The study of MAGs showed associations between NAFLD severity and some gut bacteria with microbiota functions related to hydrogen sulfide production, citrate transport, hemicellulose degradation, aldehyde production and vitamin B12 synthesis.Conclusion Using new metagenomics methods, our study unveils potential mechanisms by which certain bacteria from the gut microbiota could protect or contribute to the development of NASH and liver fibrosis in NAFLD.

Published
2021
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9. Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model

Author

Soleti, Raffaella, primary, Coué, Marine, additional, Trenteseaux, Charlotte, additional, Hilairet, Gregory, additional, Fizanne, Lionel, additional, Kasbi-Chadli, Fatima, additional, Mallegol, Patricia, additional, Chaigneau, Julien, additional, Boursier, Jerome, additional, Krempf, Michel, additional, Geoffriau, Emmanuel, additional, Andriantsitohaina, Ramaroson, additional, and Ouguerram, Khadija, additional

Published
2021
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10. Cross‐linkage between bacterial taxonomy and gene functions: a study of metagenome‐assembled genomes of gut microbiota in adult non‐alcoholic fatty liver disease

Author

Canivet, Clemence M., primary, David, Norma, additional, Pailhoriès, Helene, additional, Briand, Martial, additional, Guy, Cynthia D., additional, Bouchez, Olivier, additional, Hunault, Gilles, additional, Fizanne, Lionel, additional, Lannes, Adrien, additional, Oberti, Frederic, additional, Fouchard, Isabelle, additional, Calès, Paul, additional, Diehl, Anna Mae, additional, Barret, Matthieu, additional, and Boursier, Jerome, additional

Published
2021
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11. Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice

Author

Soleti, Raffaella, primary, Trenteseaux, Charlotte, additional, Fizanne, Lionel, additional, Coué, Marine, additional, Hilairet, Gregory, additional, Kasbi-Chadli, Fatima, additional, Mallegol, Patricia, additional, Chaigneau, Julien, additional, Boursier, Jerome, additional, Krempf, Michel, additional, Orsel, Mathilde, additional, Ouguerram, Khadija, additional, and Andriantsitohaina, Ramaroson, additional

Published
2020
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12. Supp_material_Bestion_et_al._review – Supplemental material for GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition

Author

Eloïne Bestion, Jilkova, Zuzana Macek, Jean-Louis Mège, Novello, Marie, Keerthi Kurma, Seyedeh Tayebeh Ahmad Pour, Lalmanach, Gilles, Vanderlynden, Lise, Fizanne, Lionel, Bassissi, Firas, Madani Rachid, Tracz, Jennifer, Boursier, Jérôme, Courcambeck, Jérôme, Serdjebi, Cindy, Ansaldi, Christelle, Decaens, Thomas, Halfon, Philippe, and Brun, Sonia

Subjects
FOS: Psychology, 110203 Respiratory Diseases, FOS: Clinical medicine, Cardiology, 170199 Psychology not elsewhere classified, 111702 Aged Health Care, FOS: Health sciences, 110319 Psychiatry (incl. Psychotherapy), 110306 Endocrinology, 110308 Geriatrics and Gerontology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, Supp_material_Bestion_et_al._review for GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition by Eloïne Bestion, Zuzana Macek Jilkova, Jean-Louis Mège, Marie Novello, Keerthi Kurma, Seyedeh Tayebeh Ahmad Pour, Gilles Lalmanach, Lise Vanderlynden, Lionel Fizanne, Firas Bassissi, Madani Rachid, Jennifer Tracz, Jérôme Boursier, Jérôme Courcambeck, Cindy Serdjebi, Christelle Ansaldi, Thomas Decaens, Philippe Halfon and Sonia Brun in Therapeutic Advances in Chronic Disease

Published
2020
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13. Meeting Abstract: 2143

Author

Eloine, Bestion, Lalmanach, Gilles, Novello, Marie, Macek Jilkova, Zuzana, Bassissi, Firas, Lyse, Vanderlynden, Madani, Rachid, Fizanne, Lionel, Tracz, Jennifer, Courcambeck, Jérôme, Serdjebi, Cindy, Ansaldi, Christelle, Decaens, Thomas, Halfon, Philippe, Brun, Sonia, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Trophos S.A., Rétrovirus et Maladies Associées, Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen [Fondation Ambroise Paré - Marseille], Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

16. GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition

Author

Bestion, Eloïne, primary, Jilkova, Zuzana Macek, additional, Mège, Jean-Louis, additional, Novello, Marie, additional, Kurma, Keerthi, additional, Pour, Seyedeh Tayebeh Ahmad, additional, Lalmanach, Gilles, additional, Vanderlynden, Lise, additional, Fizanne, Lionel, additional, Bassissi, Firas, additional, Rachid, Madani, additional, Tracz, Jennifer, additional, Boursier, Jérôme, additional, Courcambeck, Jérôme, additional, Serdjebi, Cindy, additional, Ansaldi, Christelle, additional, Decaens, Thomas, additional, Halfon, Philippe, additional, and Brun, Sonia, additional

Published
2020
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17. Signal processing methodology to study the cutaneous vasodilator response to a local external pressure application detected by laser Doppler flowmetry

Author

Humeau, Anne, Fizanne, Lionel, Garry, Ambroise, Saumet, Jean-Louis, and L'Huillier, Jean-Pierre

Subjects
Blood vessels -- Dilatation, Blood vessels -- Research, Biological sciences, Business, Computers, Health care industry
Abstract

The existence of a cutaneous pressure-induced vasodilation (PIV) has recently been reported. This paper proposes a signal processing methodology to improve PIV knowledge. Temporal variations of laser Doppler signals rhythmic activities are first analyzed on anesthetized rats. The results lead to a method that provides a better PIV understanding. Index Terms--Laser Doppler, microcirculation, pressure, rat, scalogram.

Published
2004

18. Metagenomic analysis shows a shift in taxonomic and functional composition of the gut microbiota in NASH patients

Author

Boursier, Jérôme, Barret, Matthieu, Macé, Julien, Hunnault, Gilles, Guy, Cynthia D., Fizanne, Lionel, Lannes, Adrien, Frederic, Oberti, Fouchard-Hubert, Isabelle, Calès, Paul, Diehl, Anna Mae, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Duke University [Durham], and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDE] Environmental Sciences, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

20. GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition.

Author

Bestion, Eloïne, Jilkova, Zuzana Macek, Mège, Jean-Louis, Novello, Marie, Kurma, Keerthi, Pour, Seyedeh Tayebeh Ahmad, Lalmanach, Gilles, Vanderlynden, Lise, Fizanne, Lionel, Bassissi, Firas, Rachid, Madani, Tracz, Jennifer, Boursier, Jérôme, Courcambeck, Jérôme, Serdjebi, Cindy, Ansaldi, Christelle, Decaens, Thomas, Halfon, Philippe, and Brun, Sonia

Abstract

Background: Hepatic fibrosis is the result of chronic liver injury that can progress to cirrhosis and lead to liver failure. Nevertheless, there are no anti-fibrotic drugs licensed for human use. Here, we investigated the anti-fibrotic activity of GNS561, a new lysosomotropic molecule with high liver tropism. Methods: The anti-fibrotic effect of GNS561 was determined in vitro using LX-2 hepatic stellate cells (HSCs) and primary human HSCs by studying cell viability, activity of caspases 3/7, autophagic flux, cathepsin maturation and activity, HSC activation and transforming growth factor-β1 (TGF-β1) maturation and signaling. The contribution of GNS561 lysosomotropism to its anti-fibrotic activity was assessed by increasing lysosomal pH. The potency of GNS561 on fibrosis was evaluated in vivo in a rat model of diethylnitrosamine-induced liver fibrosis. Results: GNS561 significantly decreased cell viability and promoted apoptosis. Disrupting the lysosomal pH gradient impaired its pharmacological effects, suggesting that GNS561 lysosomotropism mediated cell death. GNS561 impaired cathepsin activity, leading to defective TGF-β1 maturation and autophagic processes. Moreover, GNS561 decreased HSC activation and extracellular matrix deposition by downregulating TGF-β1/Smad and mitogen-activated proteine kinase signaling and inducing fibrolysis. Finally, oral administration of GNS561 (15 mg/kg per day) was well tolerated and attenuated diethylnitrosamine-induced liver fibrosis in this rat model (decrease of collagen deposition and of pro-fibrotic markers and increase of fibrolysis). Conclusion: GNS561 is a new potent lysosomotropic compound that could represent a valid medicinal option for hepatic fibrosis treatment through both its anti-fibrotic and its pro-fibrolytic effects. In addition, this study provides a rationale for targeting lysosomes as a promising therapeutic strategy in liver fibrosis. [ABSTRACT FROM AUTHOR]

Published
2020
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23. Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

Author

Uher, M, Pisarcíková, M, Filka, J, Podracká, L, Kurák, M, Ganster, Frederique, Burban, Mélanie, De La Bourdonnaye, Mathilde, Fizanne, Lionel, Douay, Olivier, Loufrani, Laurent, Mercat, Alain, Calès, Paul, Radermacher, Peter, Henrion, Daniel, Asfar, Pierre, Meziani, Ferhat, Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Expression des gènes des phosphorylations oxydatives mitochondriales. Maintenance de l'ADN MT, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire MITOVASC, UMR CNRS 6015 - INSERM 1083, Université d'Angers, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d ’ Hémodynamique, Interaction Fibrose et Invasivité tumorale hépatique, UPRES 3859, Universitätsklinikum Ulm - University Hospital of Ulm, Laboratoire HIFI, Mitochondries, stress oxydant et protection musculaire (Strasbourg), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Département de Réanimation Médicale et de Médecine Hyperbare, Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Financial support from the Association de Recherche en Réanimation Médicale et Médecine Hyperbare (Angers, France)., Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), and BMC, Ed.

Subjects
Male, Mean arterial pressure, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Resuscitation, Ischemia, Hemodynamics, Sodium hydrosulfide, Pharmacology, Shock, Hemorrhagic, Critical Care and Intensive Care Medicine, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Random Allocation, 0302 clinical medicine, medicine.artery, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Hydrogen Sulfide, Rats, Wistar, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Aorta, business.industry, Research, medicine.disease, 3. Good health, Rats, Heme oxygenase, Oxidative Stress, chemistry, Anesthesia, Shock (circulatory), medicine.symptom, Inflammation Mediators, business, 030217 neurology & neurosurgery
Abstract

International audience; IntroductionHydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses.MethodsThirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2 -) were also measured by electron paramagnetic resonance.ResultsAt the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2 - release in both aorta and heart (P < 0.05).ConclusionsNaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR).

Published
2010
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24. Linear and nonlinear analyses of laser Doppler flowmetry signals recorded during isoflurane-induced anaesthesia in healthy rats

Author

Humeau, Anne, Fizanne, Lionel, Roux, Jerôme, Asfar, Pierre, Calès, Paul, Rousseau, David, Chapeau-Blondeau, François, Laboratoire d'Ingéniérie des Systèmes Automatisés (LISA), Université d'Angers (UA), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Service Commun Animalerie hospitalo-universitaire (SCAHU), Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Institut National de Physique Nucléaire et de Physique des Particules

Published
2008

25. Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure-induced vasodilatation in rodents

Author

Fizanne, Lionel, Sigaudo-Roussel, Dominique, Saumet, Jean Louis, and Fromy, Bérengère

Subjects
Male, Dose-Response Relationship, Drug, Receptors, Vasoactive Intestinal Polypeptide, Type I, Research Papers, Peptide Fragments, Rats, Vasodilation, Mice, Pressure, Animals, Receptors, Vasoactive Intestinal Peptide, Receptors, Vasoactive Intestinal Peptide, Type II, Rats, Wistar, Vasoactive Intestinal Peptide
Abstract

A transient increase in skin blood flow in response to an innocuous local pressure application, defined as pressure-induced vasodilatation (PIV), delays the occurrence of ischaemia, suggesting a protective feature against applied pressure. The PIV response depends on capsaicin-sensitive nerve fibres and calcitonin gene-related peptide (CGRP) has been shown to be involved. In these fibres, CGRP coexists with pituitary adenylate cyclase-activating polypeptide (PACAP). Three distinct receptors mediate the biological effects of PACAP: VPAC1 and VPAC2 receptors binding with the same affinity for PACAP and vasoactive intestinal peptide and PAC1 receptors showing high selectivity for PACAP. Because the receptors are widely expressed in the nervous system and in the skin, we hypothesized that at least one of them is involved in PIV development. To verify this hypothesis, we used [D-p-Cl-Phe(6),Leu(17)]-VIP (nonspecific antagonist of VPAC1/VPAC2 receptors), PG 97-269 (antagonist of VPAC1 receptors), PACAP(6-38) (antagonist of VPAC2/PAC1 receptors) and Max.d.4 (antagonist of PAC1 receptors) in anaesthetized rodents. The blockade of VPAC1/VPAC2, VPAC1 or VPAC2/PAC1 receptors eliminated the PIV response, whereas PAC1 blockade had no effect, demonstrating an involvement of VPAC1/VPAC2 receptors in PIV development. Moreover, endothelium-independent and -dependent vasodilator responses were unchanged by the VPAC1/VPAC2 antagonist. Thus, the absence of a PIV response following VPAC1/VPAC2 blockade cannot be explained by any dysfunction of the vascular smooth muscle or endothelial vasodilator capacity. The involvement of VPAC1/VPAC2 receptors in the development of PIV seems to imply a series relationship in which each receptor type (CGRP, VPAC1, VPAC2) is necessary for the full transmission of the response.

Published
2003

26. Effect of head-upright tilt on the dynamic of cerebral autoregulation

Author

Lefthériotis, Georges, Preckel, Marie-Pierre, Fizanne, Lionel, Victor, J, Dupuis, Jean-Marc, Saumet, Jean-Louis, Univ Angers, Okina, Biologie Neurovasculaire Intégrée (BNVI), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Leg, [SDV]Life Sciences [q-bio], Posture, Doppler, Blood Pressure, Transcranial, [SDV] Life Sciences [q-bio], Carbon dioxide, Heart Rate, Regional Blood Flow, Cerebrovascular Circulation, Humans, Female, Vascular Resistance, Ultrasonography
Abstract

International audience; The effect of head-upright tilting on the rate of cerebral autoregulation was studied in 12 healthy volunteers (nine men and three women; age range 20-36 years). The dynamics of cerebral autoregulation was determined from the rate of change in cerebral resistance (RoR) during a drop in arterial blood pressure induced by rapid deflation of a 3-min ischaemic thigh cuff and from the ratio of changes in cerebral blood flow and arterial blood pressure (CAI) during the recovery period after the drop in arterial blood pressure. The test was performed supine and with 40 degrees head-up tilt (40 degrees HUT). Middle cerebral artery mean blood flow velocity was measured by transcranial Doppler simultaneously with peripheral arterial blood pressure using Finapres. The thigh cuff deflation induced a larger drop in arterial pressure during 40 degrees HUT [median -28% (25 percentile -36, 75 percentile -19)] than in the supine position [-16% (-23, -15)] (P < 0.01) and in cerebral resistance [supine: -12% (-15, -6); 40 degrees HUT: -15% (-20, -12); P < 0.05]. There was no significant change in RoR [15% s-1 (12, 15)] and CAI [1.9 (1.5, 3.1)] measured supine and during 40 degrees HUT [RoR: 13% s-1 (12, 15); CAI: 1.3 (0.99, 1.9)]. During the drop in arterial pressure, the relationship between arterial blood pressure and systolic peak-to-peak interval exhibited an hysteresis loop, indicating a cardiopulmonary and/or baroreflex activation that was not observed with cerebral resistance. The rate of autoregulation is an intrinsic property of the cerebral vascular bed and is not affected by the vasodilator state in the range of arterial blood pressure changes induced by the tight cuff method.

Published
1998

27. Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

Author

Ganster, Frédérique, primary, Burban, Mélanie, additional, de la Bourdonnaye, Mathilde, additional, Fizanne, Lionel, additional, Douay, Olivier, additional, Loufrani, Laurent, additional, Mercat, Alain, additional, Calès, Paul, additional, Radermacher, Peter, additional, Henrion, Daniel, additional, Asfar, Pierre, additional, and Meziani, Ferhat, additional

Published
2010
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28. Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats*

Author

Mortaza, Satar, primary, Martinez, M Carmen, additional, Baron-Menguy, Céline, additional, Burban, Mélanie, additional, de la Bourdonnaye, Mathilde, additional, Fizanne, Lionel, additional, Pierrot, Marc, additional, Calès, Paul, additional, Henrion, Daniel, additional, Andriantsitohaina, Ramaroson, additional, Mercat, Alain, additional, Asfar, Pierre, additional, and Meziani, Ferhat, additional

Published
2009
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32. Increasing severity of NAFLD is associated with gut dysbiosis and modification of the metabolic function of the gut microbiota

Author

Boursier, Jerome, Mueller, Olaf, Barret, Matthieu, Machado, Mariana V., Fizanne, Lionel, Guy, Cynthia D., Rawls, John F., Lawrence David, Hunault, Gilles, Oberti, Frederic, Cales, Paul, Diehl, Anna Mae, Université d'Angers (UA), Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Duke University [Durham], Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Division of Gastroenterology, Duke Clinical Research Institute-Duke University Medical Center, and American Association for the Study of Liver Diseases (AASLD). USA.

Subjects
[SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

33. Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.

Author

Moal F, Veal N, Vuillemin E, Barrière E, Wang J, Fizanne L, Oberti F, Douay O, Gallois Y, Bonnefont-Rousselot D, Rousselet MC, and Calès P

Subjects
Alkaline Phosphatase blood, Animals, Aspartate Aminotransferases blood, Bilirubin blood, Blood Pressure drug effects, Disease Models, Animal, Heart Rate drug effects, Hypertension, Portal etiology, Ligation, Lipid Peroxidation drug effects, Liver Circulation drug effects, Liver Cirrhosis etiology, Male, Nitric Oxide blood, Rats, Rats, Sprague-Dawley, Vascular Resistance drug effects, Bile Ducts physiopathology, Hypertension, Portal prevention & control, Liver Cirrhosis prevention & control, Nitric Oxide Donors pharmacology, Pyrrolidines pharmacology
Abstract

Aim: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL)., Methods: Treatment (placebo or V-PYRRO/NO 0.53 micromol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed., Results: Compared to placebo treatment, V-PYRRO/NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P<0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P=0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P<0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P=0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham-operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver., Conclusion: Continuous administrations of V-PYRRO/NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo-dynamic effects.

Published
2006
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