Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model

Nigericin is a potent antibiotic derived from Streptomyces hygroscopicus which acts as a polyether ionophore. The anticancer property of nigericin was extensively studied, and it has been proven to inhibit cancer cell proliferation, progression, and invasion in prostate, colorectal, nasopharyngeal,...

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Main Authors: Longchuan Wu, Dan Wang, Xiangfeng Qian, Arunachalam Chinnathambi, Samer Hasan Hussein-Al-Ali, Yong Yang
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Arabian Journal of Chemistry
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1878535223004343
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author Longchuan Wu
Dan Wang
Xiangfeng Qian
Arunachalam Chinnathambi
Samer Hasan Hussein-Al-Ali
Yong Yang
author_facet Longchuan Wu
Dan Wang
Xiangfeng Qian
Arunachalam Chinnathambi
Samer Hasan Hussein-Al-Ali
Yong Yang
author_sort Longchuan Wu
collection DOAJ
description Nigericin is a potent antibiotic derived from Streptomyces hygroscopicus which acts as a polyether ionophore. The anticancer property of nigericin was extensively studied, and it has been proven to inhibit cancer cell proliferation, progression, and invasion in prostate, colorectal, nasopharyngeal, and lung cancer. It also stimulates bacterial clearance in macrophages. The protective role of nigericin in sepsis, which is the foremost risk factor for acute lung injury and acute respiratory distress syndrome. Since bacteremia is frequently associated with lung injury, in this study we evaluated the potency of nigericin against an lipopolysaccharide (LPS)-induced sepsis mice model. BALB/c mice were challenged with intratracheal administration of LPS and simultaneously treated with 10 mg/kg and 20 mg/kg nigericin for 3 consecutive days. The mice were euthanized, and the lung tissue was excised to determine the lung wet/dry ratio. Bronchoalveolar lavage fluid was collected and assessed for protein content, LDH, and immune cell count. The antioxidant activity of nigericin was evaluated by measuring the MPO, MDA, SOD, and GSH activities in the lung tissues. The proinflammatory cytokines TNF-α and IL-6 were quantified to assess the anti-inflammatory potency against LPS-induced inflammation. iNOS, COX-2 and PGE-2 levels in lung tissue of nigericin-treated LPS-challenged mice were estimated to assess the immunomodulatory activity of nigericin. Finally, the antiapoptotic potency and cytoprotective effect of nigericin were analyzed by estimating apoptotic protein levels in lung tissue and assessing lung tissue histopathology with hematoxylin & eosin staining. Nigericin treatment significantly reduced immune cell infiltration, synthesis of proinflammatory cytokines, immunomodulatory proteins, and proapoptotic proteins in LPS-challenged mice. It also increased antioxidants and antiapoptotic protein Bcl2, thereby ameliorating lung tissue from LPS-induced inflammation. Our results indicate nigericin suppressed the LPS induced sepsis in an in vivo model and has the therapeutic potency to cure sepsis induced acute lung injury.
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spelling doaj.art-ca85274447714c2e8c13646e6e514f892023-06-15T04:55:07ZengElsevierArabian Journal of Chemistry1878-53522023-08-01168104972Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo modelLongchuan Wu0Dan Wang1Xiangfeng Qian2Arunachalam Chinnathambi3Samer Hasan Hussein-Al-Ali4Yong Yang5Department of Emergency, The first people's Hospital of Linping District, Hangzhou, Zhejiang 311100, ChinaPharmaceutical Department, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei 430060, ChinaDepartment of Emergency, The first people's Hospital of Linping District, Hangzhou, Zhejiang 311100, ChinaDepartment of Botany and Microbiology, College of Science, King Saud University, PO Box -2455, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Isra University, Amman 11622, JordanDepartment of Critical Care Medicine, Changsha Central Hospital, University of South China, Changsha, Hunan 410004, China; Corresponding author.Nigericin is a potent antibiotic derived from Streptomyces hygroscopicus which acts as a polyether ionophore. The anticancer property of nigericin was extensively studied, and it has been proven to inhibit cancer cell proliferation, progression, and invasion in prostate, colorectal, nasopharyngeal, and lung cancer. It also stimulates bacterial clearance in macrophages. The protective role of nigericin in sepsis, which is the foremost risk factor for acute lung injury and acute respiratory distress syndrome. Since bacteremia is frequently associated with lung injury, in this study we evaluated the potency of nigericin against an lipopolysaccharide (LPS)-induced sepsis mice model. BALB/c mice were challenged with intratracheal administration of LPS and simultaneously treated with 10 mg/kg and 20 mg/kg nigericin for 3 consecutive days. The mice were euthanized, and the lung tissue was excised to determine the lung wet/dry ratio. Bronchoalveolar lavage fluid was collected and assessed for protein content, LDH, and immune cell count. The antioxidant activity of nigericin was evaluated by measuring the MPO, MDA, SOD, and GSH activities in the lung tissues. The proinflammatory cytokines TNF-α and IL-6 were quantified to assess the anti-inflammatory potency against LPS-induced inflammation. iNOS, COX-2 and PGE-2 levels in lung tissue of nigericin-treated LPS-challenged mice were estimated to assess the immunomodulatory activity of nigericin. Finally, the antiapoptotic potency and cytoprotective effect of nigericin were analyzed by estimating apoptotic protein levels in lung tissue and assessing lung tissue histopathology with hematoxylin & eosin staining. Nigericin treatment significantly reduced immune cell infiltration, synthesis of proinflammatory cytokines, immunomodulatory proteins, and proapoptotic proteins in LPS-challenged mice. It also increased antioxidants and antiapoptotic protein Bcl2, thereby ameliorating lung tissue from LPS-induced inflammation. Our results indicate nigericin suppressed the LPS induced sepsis in an in vivo model and has the therapeutic potency to cure sepsis induced acute lung injury.http://www.sciencedirect.com/science/article/pii/S1878535223004343SepsisAcute lung injuryLipopolysaccharidesInflammationAntibioticNigericin
spellingShingle Longchuan Wu
Dan Wang
Xiangfeng Qian
Arunachalam Chinnathambi
Samer Hasan Hussein-Al-Ali
Yong Yang
Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
Arabian Journal of Chemistry
Sepsis
Acute lung injury
Lipopolysaccharides
Inflammation
Antibiotic
Nigericin
title Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
title_full Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
title_fullStr Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
title_full_unstemmed Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
title_short Nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
title_sort nigericin attenuates lipopolysaccharides induced sepsis and alleviates acute lung injury in in vivo model
topic Sepsis
Acute lung injury
Lipopolysaccharides
Inflammation
Antibiotic
Nigericin
url http://www.sciencedirect.com/science/article/pii/S1878535223004343
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