Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats

Barut, Figen; Özaçmak, Veysel Haktan; TURAN, İnci; Özaçmak, Hale Sayan; Aktunç, Erol

doi:10.25011/cim.v39i1.26326

Cited by 21 publications

(24 citation statements)

References 40 publications

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“…8C ). The data above further indicated that LPS induced acute lung injury due to NOx, MPO and iNOS acceleration, which was in line with previous studies ( 36 , 37 ). ST1926, at least partly, could ameliorate LPS-induced acute lung injury by downregulating the activity of these factors.…”

Section: Resultssupporting

confidence: 92%

Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Ιnhibition by ST1926

Dong

Yuan

2018

Int J Mol Med

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Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been well developed and investigated in clinical trials for many diseases. The aim of our study was to explore the role of ST1926 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to reveal the possible molecular mechanism. Mice were treated with LPS to induce acute lung injury followed by ST1926 administration. After LPS induction, mice administered with ST1926 showed lower inflammation infiltration in bronchoalveolar lavage (BAL) fluid, and pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-18, IL-6 and tumor necrosis factor-α (TNF-α) in serum and lung tissue samples obtained from mice. In addition, western blot assays suggested that ST1926 suppressed nuclear factor-κB (NF-κB), inhibitor-κB kinase-α (IκBα) and IκB kinase (IKKα), as well as Toll-like receptor 4 (TLR4) induced by LPS. In addition, reactive oxygen species (ROS) stimulated by LPS was also suppressed for ST1926 through inhibiting p38 and extracellular receptor kinase (ERK) signaling pathway. Taken together, the data here indicated that ST1926 may be of potential value in treating acute lung injury through inflammation and ROS suppression via inactivating TLR4/NF-κB and p38/ERK1/2 signaling pathways.

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Section: Resultssupporting

confidence: 92%

Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Ιnhibition by ST1926

Dong

Yuan

2018

Int J Mol Med

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“…We observed a significant increase in LOOH formation, a byproduct of lipid peroxidation, in the four organs that were studied. Increases in lipid peroxidation have been reported after intestinal IR in such organs as the intestine (Turan et al, 2017), liver (Saidi et al, 2017), and lungs (Barut et al, 2016). Despite these deleterious effects of IR in the ischemic group in the present study, the levels of LOOH in the ileum, lungs, and liver in the IT group that was treated with curcumin remained similar to the control group.…”

Section: Discussionsupporting

confidence: 41%

Remote organs respond differently to curcumin treatment after intestinal ischemia/reperfusion injury

Bringhentti

Borges

Neves

et al. 2020

RSD

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We aimed investigate the effects of 45 min of ischemia followed by 72 h of intestinal reperfusion (IR) in the ileum, liver, lungs, and kidneys in Wistar rats and the responses of these organs to curcumin treatment. Ischemia was induced by occluding the superior mesenteric artery. Rats were treated orally with 40 mg/kg curcumin. We analyzed oxidative stress and inflammation in the ileum, liver, lungs, and kidneys. Intestinal IR led to a reduction of reduced glutathione levels in the intestine, lungs, and kidneys and increased lipid hydroperoxide levels in all organs. An increase in the enzymatic activity of catalase was observed in all organs, and an increase in superoxide dismutase activity was observed in the ileum and lungs. Glutathione s-transferase levels increased only in the kidneys. Myeloperoxidase increased in all four organs, and n-acetyl-glycosaminidase increased only in the ileum and lungs. Curcumin prevented all of the changes in the ileum and liver. In the lungs, curcumin had no effect on n-acetyl-glycosaminidase. Curcumin did not prevent the changes in reduced glutathione, lipid hydroperoxides, or myeloperoxidase in the kidneys. Intestinal IR caused oxidative stress and inflammation in the ileum, lungs, and kidneys and to a lesser degree in the liver. Because of its systemic distribution, curcumin prevented changes mainly in the ileum, lungs, and liver and to a lesser degree in the kidneys.

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“…For example, a predicted link connected the drug "Spironolactone" (DrugBank ID: DB00421) and the target "Glutathione synthetase" (DrugBank ID: BE0000185) with a score of 23.62. In a study aiming to reduce acute lung injury, Barut et al studied the effect of spironolactone administration [2]. An increased production of reduced glutathione (being a product of glutathione synthetase) has occurred in the presence of spironolactone.…”

Section: Preliminary Resultsmentioning

confidence: 99%

Computational Approaches for Drug Repositioning

Boudin

2020

Proceedings of the 29th ACM International Conference on Information &Amp; Knowledge Management

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Drug development is a costly and time consuming activity. The traditional process relies on extensive experimental efforts to map out the relevant part of the chemical space. Data about molecules, diseases, genes and other entities are present on many isolated databases, be that internal or external and in heterogeneous formats. They either require costly and inflexible data integration, or time-consuming workflows. Computational approaches, and more recently artificial intelligence based techniques, have emerged as a promising alternative for reducing the development cycle through drug repositioning. Knowledge bases are used to predict new links between old drugs and new targets. We present below the overall approach adopted for my PhD thesis, for a more holistic knowledge graph-based drug repositioning that aims to discover hidden or missing links between existing drugs and targets for which no known treatment is available. Currently, eight data and knowledge resources have already been integrated into the designed knowledge graph. CCS CONCEPTS • Information systems → Information retrieval; • Computing methodologies → Machine learning approaches; • Applied computing → Life and medical sciences.

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Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats

Cited by 21 publications

References 40 publications

Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Ιnhibition by ST1926

Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Ιnhibition by ST1926

Remote organs respond differently to curcumin treatment after intestinal ischemia/reperfusion injury

Computational Approaches for Drug Repositioning

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