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A new acyl derivative of sulfadimethoxine inhibits phagocyte oxidative burst and ameliorates inflammation in a mice model of zymosan-induced generalised inflammation

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dc.contributor.author Tariq, Ahmad Baig
dc.contributor.author Haroon, M. Haniffa
dc.contributor.author Hina, Siddiqui
dc.contributor.author Syeda, Farah Shah
dc.contributor.author Jabeen, Almas
dc.date.accessioned 2023-11-24T03:36:06Z
dc.date.available 2023-11-24T03:36:06Z
dc.date.issued 2023-11-16
dc.identifier.citation Inflammopharmacology 2023 en_US
dc.identifier.issn 1568-5608
dc.identifier.uri https://doi.org/10.1007/s10787-023-01372-0
dc.identifier.uri http://ir.lib.seu.ac.lk/handle/123456789/6841
dc.description.abstract Chronic inflammation and oxidative stress play a pivotal role in the pathophysiology of most challenging illnesses, including cancer, Alzheimer’s, cardiovascular and autoimmune diseases. The present study aimed to investigate the anti-inflammatory potential of a new sulfadimethoxine derivative N-(4-(N-(2,6-dimethoxypyrimidin-4-yl) sulfamoyl) phenyl) dodecanamide (MHH-II-32). The compound was characterised by applying 1H-, 13C-NMR, EI–MS and HRFAB–MS spectroscopic techniques. The compound inhibited zymosan-induced oxidative bursts from whole blood phagocytes and isolated polymorphonuclear cells with an IC50 value of (2.5 ± 0.4 and 3.4 ± 0.3 µg/mL), respectively. Furthermore, the inhibition of nitric oxide with an IC50 (3.6 ± 2.2 µg/mL) from lipopolysaccharide-induced J774.2 macrophages indicates its in vitro anti-inflammatory efficacy. The compound did not show toxicity towards normal fibroblast cells. The observational findings, gross anatomical analysis of visceral organs and serological tests revealed the non-toxicity of the compound at the highest tested intraperitoneal (IP) dose of 100 mg/kg in acute toxicological studies in Balb/c mice. The compound treatment (100 mg/kg) (SC) significantly (P < 0.001) downregulated the mRNA expression of inflammatory markers TNF-α, IL-1β, IL-2, IL-13, and NF-κB, which were elevated in zymosan-induced generalised inflammation (IP) in Balb/c mice while upregulated the expression of anti-inflammatory cytokine IL-10, which was reduced in zymosan-treated mice. No suppressive effect was observed at the dose of 25 mg/kg. Ibuprofen was taken as a standard drug. The results revealed that the new acyl derivative of sulfadimethoxine has an immunomodulatory effect against generalised inflammatory response with non-toxicity both in vitro and in vivo, and has therapeutic potential for various chronic inflammatory illnesses. en_US
dc.language.iso en_US en_US
dc.publisher Springer en_US
dc.subject Anti-inflammatory en_US
dc.subject Zymosan en_US
dc.subject Oxidative burst en_US
dc.subject Sulfadimethoxine en_US
dc.subject Cytokines en_US
dc.subject Nitric oxide en_US
dc.title A new acyl derivative of sulfadimethoxine inhibits phagocyte oxidative burst and ameliorates inflammation in a mice model of zymosan-induced generalised inflammation en_US
dc.type Article en_US


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    THESE ARE RESEARCH ARTICLES OF ACADEMIC STAFF, PUBLISHED IN JOURNALS AND PROCEEDINGS ELSWHERE

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