Effects of Nintedanib in an Animal Model of Liver Fibrosis
Identifieur interne : 000411 ( Main/Exploration ); précédent : 000410; suivant : 000412Effects of Nintedanib in an Animal Model of Liver Fibrosis
Auteurs : Lutz Wollin [Allemagne] ; Dieudonnée Togbe [France] ; Bernhard Ryffel [France]Source :
- BioMed Research International [ 2314-6133 ] ; 2020.
Abstract
Systemic sclerosis can affect multiple internal organs, including the liver and lungs. Nintedanib, an antifibrotic approved for treatment of interstitial lung disease associated with systemic sclerosis, may have activity outside of the lungs. This study explored the effect of preventive and therapeutic nintedanib treatment in a 3-week carbon tetrachloride (CCL4)-induced (500 mg/kg/day twice weekly for 3 weeks) model of hepatic inflammation and fibrosis in C57Bl/6 mice (aged 8 weeks,
Url:
DOI: 10.1155/2020/3867198
PubMed: 32337244
PubMed Central: 7150695
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000967
- to stream Pmc, to step Curation: 000967
- to stream Pmc, to step Checkpoint: 000285
- to stream Ncbi, to step Merge: 002C66
- to stream Ncbi, to step Curation: 002C66
- to stream Ncbi, to step Checkpoint: 002C66
- to stream Main, to step Merge: 000411
- to stream Main, to step Curation: 000411
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of Nintedanib in an Animal Model of Liver Fibrosis</title><author><name sortKey="Wollin, Lutz" sort="Wollin, Lutz" uniqKey="Wollin L" first="Lutz" last="Wollin">Lutz Wollin</name><affiliation wicri:level="1"><nlm:aff id="I1">Immunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach 88397, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Immunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach 88397</wicri:regionArea><wicri:noRegion>88397</wicri:noRegion><wicri:noRegion>88397</wicri:noRegion><wicri:noRegion>Biberach 88397</wicri:noRegion></affiliation></author><author><name sortKey="Togbe, Dieudonnee" sort="Togbe, Dieudonnee" uniqKey="Togbe D" first="Dieudonnée" last="Togbe">Dieudonnée Togbe</name><affiliation wicri:level="3"><nlm:aff id="I2">Research and Development Department, Artimmune, Orléans 45100, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research and Development Department, Artimmune, Orléans 45100</wicri:regionArea><placeName><region type="region" nuts="2">Centre-Val de Loire</region><region type="old region" nuts="2">Région Centre</region></placeName></affiliation></author><author><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name><affiliation wicri:level="3"><nlm:aff id="I3">Molecular Immunology, INEM, UMR7355, CNRS and University Orléans, Orléans 45071, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Molecular Immunology, INEM, UMR7355, CNRS and University Orléans, Orléans 45071</wicri:regionArea><placeName><region type="region" nuts="2">Centre-Val de Loire</region><region type="old region" nuts="2">Région Centre</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32337244</idno><idno type="pmc">7150695</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150695</idno><idno type="RBID">PMC:7150695</idno><idno type="doi">10.1155/2020/3867198</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000967</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000967</idno><idno type="wicri:Area/Pmc/Curation">000967</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000967</idno><idno type="wicri:Area/Pmc/Checkpoint">000285</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000285</idno><idno type="wicri:Area/Ncbi/Merge">002C66</idno><idno type="wicri:Area/Ncbi/Curation">002C66</idno><idno type="wicri:Area/Ncbi/Checkpoint">002C66</idno><idno type="wicri:doubleKey">2314-6133:2020:Wollin L:effects:of:nintedanib</idno><idno type="wicri:Area/Main/Merge">000411</idno><idno type="wicri:Area/Main/Curation">000411</idno><idno type="wicri:Area/Main/Exploration">000411</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effects of Nintedanib in an Animal Model of Liver Fibrosis</title><author><name sortKey="Wollin, Lutz" sort="Wollin, Lutz" uniqKey="Wollin L" first="Lutz" last="Wollin">Lutz Wollin</name><affiliation wicri:level="1"><nlm:aff id="I1">Immunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach 88397, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Immunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach 88397</wicri:regionArea><wicri:noRegion>88397</wicri:noRegion><wicri:noRegion>88397</wicri:noRegion><wicri:noRegion>Biberach 88397</wicri:noRegion></affiliation></author><author><name sortKey="Togbe, Dieudonnee" sort="Togbe, Dieudonnee" uniqKey="Togbe D" first="Dieudonnée" last="Togbe">Dieudonnée Togbe</name><affiliation wicri:level="3"><nlm:aff id="I2">Research and Development Department, Artimmune, Orléans 45100, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research and Development Department, Artimmune, Orléans 45100</wicri:regionArea><placeName><region type="region" nuts="2">Centre-Val de Loire</region><region type="old region" nuts="2">Région Centre</region></placeName></affiliation></author><author><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name><affiliation wicri:level="3"><nlm:aff id="I3">Molecular Immunology, INEM, UMR7355, CNRS and University Orléans, Orléans 45071, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Molecular Immunology, INEM, UMR7355, CNRS and University Orléans, Orléans 45071</wicri:regionArea><placeName><region type="region" nuts="2">Centre-Val de Loire</region><region type="old region" nuts="2">Région Centre</region></placeName></affiliation></author></analytic><series><title level="j">BioMed Research International</title><idno type="ISSN">2314-6133</idno><idno type="eISSN">2314-6141</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Systemic sclerosis can affect multiple internal organs, including the liver and lungs. Nintedanib, an antifibrotic approved for treatment of interstitial lung disease associated with systemic sclerosis, may have activity outside of the lungs. This study explored the effect of preventive and therapeutic nintedanib treatment in a 3-week carbon tetrachloride (CCL<sub>4</sub>)-induced (500 mg/kg/day twice weekly for 3 weeks) model of hepatic inflammation and fibrosis in C57Bl/6 mice (aged 8 weeks, <italic>n</italic> = 5 per group). Mice also received nintedanib (30 or 60 mg/kg/day) either each day for 21 days (preventive treatment) or from day 7 or day 14 (therapeutic treatment). Preventive nintedanib treatment at both doses significantly reduced CCL<sub>4</sub>-induced increases in myeloperoxidase (<italic>p</italic> < 0.01), hepatic collagen (<italic>p</italic> < 0.001), and interleukin (IL)-6 (<italic>p</italic> < 0.01) in the liver. Nintedanib also significantly reduced hepatic necrosis (<italic>p</italic> < 0.01 and <italic>p</italic> < 0.05), inflammation (<italic>p</italic> < 0.001 and <italic>p</italic> < 0.05), fibrosis (<italic>p</italic> < 0.001 and <italic>p</italic> < 0.05) and IL-1<italic>β</italic> (<italic>p</italic> < 0.05 and <italic>p</italic> < 0.001) at both 30 and 60 mg/kg/day, respectively. Therapeutic treatment with nintedanib at 30 and 60 mg/kg/day significantly reduced CCL<sub>4</sub>-induced serum alanine aminotransferase from day 7 (<italic>p</italic> < 0.05 and <italic>p</italic> < 0.001) and day 14 (<italic>p</italic> < 0.01 and <italic>p</italic> < 0.05), respectively. Increases in tissue inhibitor of metalloproteinase-1 were significantly reduced by nintedanib at 60 mg/kg/day from day 7 only (<italic>p</italic> < 0.001), and nintedanib completely blocked elevation of IL-6 and IL-1<italic>β</italic> levels regardless of dose or start of treatment (<italic>p</italic> < 0.05–<italic>p</italic> < 0.001). In both the preventive and therapeutic treatment schedules of the study, nintedanib treatment was beneficial in attenuating CCL<sub>4</sub>-induced pathology and reducing hepatic injury, inflammation, and fibrosis, demonstrating that nintedanib has antifibrotic and anti-inflammatory activity outside of the lungs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Seki, E" uniqKey="Seki E">E. Seki</name></author><author><name sortKey="De Minicis, S" uniqKey="De Minicis S">S. de Minicis</name></author><author><name sortKey="Osterreicher, C H" uniqKey="Osterreicher C">C. H. Österreicher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilberg, F" uniqKey="Hilberg F">F. Hilberg</name></author><author><name sortKey="Roth, G J" uniqKey="Roth G">G. J. Roth</name></author><author><name sortKey="Krssak, M" uniqKey="Krssak M">M. Krssak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varga, J" uniqKey="Varga J">J. Varga</name></author><author><name sortKey="Trojanowska, M" uniqKey="Trojanowska M">M. Trojanowska</name></author><author><name sortKey="Kuwana, M" uniqKey="Kuwana M">M. Kuwana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denton, C P" uniqKey="Denton C">C. P. Denton</name></author><author><name sortKey="Khanna, D" uniqKey="Khanna D">D. Khanna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaeger, V K" uniqKey="Jaeger V">V. K. Jaeger</name></author><author><name sortKey="Wirz, E G" uniqKey="Wirz E">E. G. Wirz</name></author><author><name sortKey="Allanore, Y" uniqKey="Allanore Y">Y. Allanore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frech, T M" uniqKey="Frech T">T. M. Frech</name></author><author><name sortKey="Mar, D" uniqKey="Mar D">D. Mar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L. Richeldi</name></author><author><name sortKey="Du Bois, R M" uniqKey="Du Bois R">R. M. du Bois</name></author><author><name sortKey="Raghu, G" uniqKey="Raghu G">G. Raghu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L. Richeldi</name></author><author><name sortKey="Costabel, U" uniqKey="Costabel U">U. Costabel</name></author><author><name sortKey="Selman, M" uniqKey="Selman M">M. Selman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L. Richeldi</name></author><author><name sortKey="Cottin, V" uniqKey="Cottin V">V. Cottin</name></author><author><name sortKey="Du Bois, R M" uniqKey="Du Bois R">R. M. du Bois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goh, N S" uniqKey="Goh N">N. S. Goh</name></author><author><name sortKey="Desai, S R" uniqKey="Desai S">S. R. Desai</name></author><author><name sortKey="Veeraraghavan, S" uniqKey="Veeraraghavan S">S. Veeraraghavan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goh, N S" uniqKey="Goh N">N. S. Goh</name></author><author><name sortKey="Hoyles, R K" uniqKey="Hoyles R">R. K. Hoyles</name></author><author><name sortKey="Denton, C P" uniqKey="Denton C">C. P. Denton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Distler, O" uniqKey="Distler O">O. Distler</name></author><author><name sortKey="Highland, K B" uniqKey="Highland K">K. B. Highland</name></author><author><name sortKey="Gahlemann, M" uniqKey="Gahlemann M">M. Gahlemann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flaherty, K R" uniqKey="Flaherty K">K. R. Flaherty</name></author><author><name sortKey="Wells, A U" uniqKey="Wells A">A. U. Wells</name></author><author><name sortKey="Cottin, V" uniqKey="Cottin V">V. Cottin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chentoufi, A A" uniqKey="Chentoufi A">A. A. Chentoufi</name></author><author><name sortKey="Serov, Y A" uniqKey="Serov Y">Y. A. Serov</name></author><author><name sortKey="Alazmi, M" uniqKey="Alazmi M">M. Alazmi</name></author><author><name sortKey="Baba, K" uniqKey="Baba K">K. Baba</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ozturk Akcora, B" uniqKey="Ozturk Akcora B">B. Ozturk Akcora</name></author><author><name sortKey="Storm, G" uniqKey="Storm G">G. Storm</name></author><author><name sortKey="Prakash, J" uniqKey="Prakash J">J. Prakash</name></author><author><name sortKey="Bansal, R" uniqKey="Bansal R">R. Bansal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lisbonne, M" uniqKey="Lisbonne M">M. Lisbonne</name></author><author><name sortKey="L Helgoualc H, A" uniqKey="L Helgoualc H A">A. L'Helgoualc'h</name></author><author><name sortKey="Nauwelaers, G" uniqKey="Nauwelaers G">G. Nauwelaers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Susutlertpanya, W" uniqKey="Susutlertpanya W">W. Susutlertpanya</name></author><author><name sortKey="Wakuda, H" uniqKey="Wakuda H">H. Wakuda</name></author><author><name sortKey="Otani, N" uniqKey="Otani N">N. Otani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Conway, R" uniqKey="Conway R">R. Conway</name></author><author><name sortKey="Carey, J J" uniqKey="Carey J">J. J. Carey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wollin, L" uniqKey="Wollin L">L. Wollin</name></author><author><name sortKey="Maillet, I" uniqKey="Maillet I">I. Maillet</name></author><author><name sortKey="Quesniaux, V" uniqKey="Quesniaux V">V. Quesniaux</name></author><author><name sortKey="Holweg, A" uniqKey="Holweg A">A. Holweg</name></author><author><name sortKey="Ryffel, B" uniqKey="Ryffel B">B. Ryffel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, M" uniqKey="Shaw M">M. Shaw</name></author><author><name sortKey="Collins, B F" uniqKey="Collins B">B. F. Collins</name></author><author><name sortKey="Ho, L A" uniqKey="Ho L">L. A. Ho</name></author><author><name sortKey="Raghu, G" uniqKey="Raghu G">G. Raghu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rubbert Roth, A" uniqKey="Rubbert Roth A">A. Rubbert-Roth</name></author><author><name sortKey="Furst, D E" uniqKey="Furst D">D. E. Furst</name></author><author><name sortKey="Nebesky, J M" uniqKey="Nebesky J">J. M. Nebesky</name></author><author><name sortKey="Jin, A" uniqKey="Jin A">A. Jin</name></author><author><name sortKey="Berber, E" uniqKey="Berber E">E. Berber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuo, C S" uniqKey="Kuo C">C. S. Kuo</name></author><author><name sortKey="Young, L R" uniqKey="Young L">L. R. Young</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>France</li></country><region><li>Centre-Val de Loire</li><li>Région Centre</li></region></list><tree><country name="Allemagne"><noRegion><name sortKey="Wollin, Lutz" sort="Wollin, Lutz" uniqKey="Wollin L" first="Lutz" last="Wollin">Lutz Wollin</name></noRegion></country><country name="France"><region name="Centre-Val de Loire"><name sortKey="Togbe, Dieudonnee" sort="Togbe, Dieudonnee" uniqKey="Togbe D" first="Dieudonnée" last="Togbe">Dieudonnée Togbe</name></region><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/TocilizumabV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000411 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000411 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= TocilizumabV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:7150695
|texte= Effects of Nintedanib in an Animal Model of Liver Fibrosis
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32337244" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a TocilizumabV1
| This area was generated with Dilib version V0.6.34. |  |