Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediato

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(2020) 21:81

RESEARCH ARTICLE

Open Access

Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression Hassan Ali†, Ashrafullah Khan†, Jawad Ali, Hadayat Ullah, Adnan Khan, Hussain Ali, Nadeem Irshad and Salman Khan*

Abstract Background: Acute lung injury (ALI) together with acute respiratory distress syndrome (ARDS) are associated with high rate of mortality and morbidity in patients. In the current study, the anti-inflammatory effects of continentalic acid (CNT) in LPS-induced acute lung injury model was explored. Methods: The acute lung injury model was established by administering LPS (5 mg/kg) intraperitonealy. Following LPS administration, the survival rate, temperature changes and lung Wet/Dry ratio were assessed. The antioxidants (GSH, GST, Catalase and SOD) and oxidative stress markers (MDA, NO, MPO) were evaluated in all the treated groups. Similarly, the cytokines such as IL-1β, IL-6 and TNF-α were analyzed using ELISA assay. The histological changes were determined using H and E staining, while Nrf2 and iNOS level were determined using immunohistochemistry analysis. The molecular docking analysis was performed to assess the pharmacokinetics parameters and interaction of the CNT with various protein targets. (Continued on next page)

* Correspondence: [email protected]; [email protected] † Hassan Ali and Ashrafullah Khan contributed equally to this work. Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Ali et al. BMC Pharmacology and Toxicology

(2020) 21:81

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Results: The results showed that CNT dose dependently (10, 50 and 100 mg/kg) reduced mortality rate, body temperature and lungs Wet/Dry ratio. CNT post-treatment significantly inhibited LPS-induced production of proinflammatory cytokin