Effect of OTR4120 on pulmonary fibrosis

Author:

Charef Said,Charef Najat Mejdoubi,Chiappini FranckORCID,Papy-Garcia Dulce,Barritault Denis

Abstract

AbstractBackgroundAcute respiratory distress syndrome (ARDS) can be related to airway remodeling caused by pulmonary fibrosis and systemic inflammation. Etiologies of ARDS are multifaceted such as idiopathic pulmonary fibrosis or as recently the SARS-CoV-2 infection. Antifibrotic drugs may be a better approach to slow the fibrotic process but they often have poor efficacy in patients, and the mortality rate remains high, up to 40% within 5 years of diagnosis.Here, we tested the antifibrotic effect of a ReGeneTaring Agents named OTR4120 in a bleomycin-induced mouse model of pulmonary fibrosis.MethodsSwiss mice were randomly divided into four experimental groups: saline-treated control group, an OTR4120 group, a bleomycin-induced fibrosis group without OTR4120, and a bleomycin-induced fibrosis groups with OTR4120 (intravenous injections every 3 days starting at day 11 post bleomycin I.P. injection). Lungs were compared using the lung/body weight index, and the extend of interstitial injury area was graded using histopathological assessment of haematoxylin & eosin-stained lung tissue sections. Lung tissue Collagen I and Collagen III levels, and blood cytokine levels were measured using a Collagen colorimetric kit and a Cytokine colorimetric kit, respectively.ResultsThe group treated by OTR4120 alone were used as a control. The clincal signs in all animals resoved gradually on day 17 after bleomycin injections and 6 days after OTR4120 treatment, and disappeared almost completetly at day 24 after bleomycin injections and day 13 after OTR4120 treatment. Lung/body weight index values were significantly lower in the bleomycin-OTR4120 treated group versus the bleomycin group (7.31, 9.97 and 7.63 mg/g, p-value< 0.01; respectively). Histopathological analyses suggest that OTR4120 treatment ameliorated the increased inflammatory cell infiltration, and attenuated the reduction in interstitial thickening, associated with bleomycin-induced fibrosis. Collagen III and cytokine levels were decreased in the OTR4120 group versus the fibrotic (bleomycin only) group. OTR4120-treated animals were less affected in their behavior, did not loose weight nor appetite, and recovered overall activities within 6 days of OTR4120 treatment, while none of the vehicle-treated animals recovered to normal.ConclusionOTR4120 is a potential candidate to reduce lung fibrosis.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3