Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats
Aim: To demonstrate the possible protective efficacy of nintedanib, a tyrosine kinase inhibitor with demonstrated antifibrotic and antitumor activity, in a model of acute lung injury (ALI), a severe lung disease, through NLR family pyrin domain containing 3 (NLRP3) and nuclear factor kappa B (NF-κB)...
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| Format: | Article |
| Language: | English |
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Galenos Yayincilik
2024-03-01
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| Series: | Namık Kemal Tıp Dergisi |
| Subjects: | |
| Online Access: |
http://namikkemalmedj.com/archives/archive-detail/article-preview/effects-of-nintedanib-on-the-lungs-via-nlrp3-in-a-/64770
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| author | Gulchin TANRİVERDİYEVA Pelin AYDIN Erdem TOKTAY Elif ÇADIRCI Zekai HALICI |
| author_facet | Gulchin TANRİVERDİYEVA Pelin AYDIN Erdem TOKTAY Elif ÇADIRCI Zekai HALICI |
| author_sort | Gulchin TANRİVERDİYEVA |
| collection | DOAJ |
| description | Aim: To demonstrate the possible protective efficacy of nintedanib, a tyrosine kinase inhibitor with demonstrated antifibrotic and antitumor activity, in a model of acute lung injury (ALI), a severe lung disease, through NLR family pyrin domain containing 3 (NLRP3) and nuclear factor kappa B (NF-κB) pathways. Materials and Methods: In this study, 40 male Wistar albino rats were used. These rats were divided into 5 groups of equal sizes. Before the experiment began, nintedanib was administered orally to selected groups at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg. At 24 hours, 12 hours, or 1 hour after nintedanib administration, rats selected for the lung injury model were administered intratracheal LPS. Interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) amounts were measured by ELISA method and NLRP3, caspase-1, IL-1β and NF-kB gene expressions were measured by reverse-transcriptase polymerase chain reaction. Results: It was observed that administration of nintedanib lowered the elevated NLRP3, caspase-1, IL-1β, and NF-κB expressions and the IL-1β and TNF-α cytokine levels in the tissues of rats with LPS-induced ALI. The findings obtained for the rats included in the lung injury group that received 50 mg/kg nintedanib were most similar to those of the healthy control group. Conclusion: In rats modeled with ALI, nintedanib was shown to modulate the NLRP3/NF-κB signaling pathway and reduce the effects of ALI. |
| first_indexed | 2024-04-24T19:37:56Z |
| format | Article |
| id | doaj.art-cde3955719d0427e9b6344cca0354466 |
| institution | Directory Open Access Journal |
| issn | 2587-0262 |
| language | English |
| last_indexed | 2024-04-24T19:37:56Z |
| publishDate | 2024-03-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | Namık Kemal Tıp Dergisi |
| spelling | doaj.art-cde3955719d0427e9b6344cca03544662024-03-25T11:38:44ZengGalenos YayincilikNamık Kemal Tıp Dergisi2587-02622024-03-0112181610.4274/nkmj.galenos.2024.7759813049054Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in RatsGulchin TANRİVERDİYEVA0Pelin AYDIN1Erdem TOKTAY2Elif ÇADIRCI3Zekai HALICI4 Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Kafkas Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Aim: To demonstrate the possible protective efficacy of nintedanib, a tyrosine kinase inhibitor with demonstrated antifibrotic and antitumor activity, in a model of acute lung injury (ALI), a severe lung disease, through NLR family pyrin domain containing 3 (NLRP3) and nuclear factor kappa B (NF-κB) pathways. Materials and Methods: In this study, 40 male Wistar albino rats were used. These rats were divided into 5 groups of equal sizes. Before the experiment began, nintedanib was administered orally to selected groups at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg. At 24 hours, 12 hours, or 1 hour after nintedanib administration, rats selected for the lung injury model were administered intratracheal LPS. Interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) amounts were measured by ELISA method and NLRP3, caspase-1, IL-1β and NF-kB gene expressions were measured by reverse-transcriptase polymerase chain reaction. Results: It was observed that administration of nintedanib lowered the elevated NLRP3, caspase-1, IL-1β, and NF-κB expressions and the IL-1β and TNF-α cytokine levels in the tissues of rats with LPS-induced ALI. The findings obtained for the rats included in the lung injury group that received 50 mg/kg nintedanib were most similar to those of the healthy control group. Conclusion: In rats modeled with ALI, nintedanib was shown to modulate the NLRP3/NF-κB signaling pathway and reduce the effects of ALI. http://namikkemalmedj.com/archives/archive-detail/article-preview/effects-of-nintedanib-on-the-lungs-via-nlrp3-in-a-/64770 alinf-κbnintedanibnlrp3tyrosine kinase inhibitor |
| spellingShingle | Gulchin TANRİVERDİYEVA Pelin AYDIN Erdem TOKTAY Elif ÇADIRCI Zekai HALICI Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats Namık Kemal Tıp Dergisi ali nf-κb nintedanib nlrp3 tyrosine kinase inhibitor |
| title | Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats |
| title_full | Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats |
| title_fullStr | Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats |
| title_full_unstemmed | Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats |
| title_short | Effects of Nintedanib on the Lungs via NLRP3 in a Model of Lipopolysaccharide-induced Acute Lung Injury in Rats |
| title_sort | effects of nintedanib on the lungs via nlrp3 in a model of lipopolysaccharide induced acute lung injury in rats |
| topic | ali nf-κb nintedanib nlrp3 tyrosine kinase inhibitor |
| url |
http://namikkemalmedj.com/archives/archive-detail/article-preview/effects-of-nintedanib-on-the-lungs-via-nlrp3-in-a-/64770
|
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