The present study was carried out to determine the effect of cyclooxygenase-2 (COX-2) inhibitor on acid aspiration-induced lung injury in rats. Rats were allocated into one of four groups. Group H received intratracheal instillation of HCl. Group S received saline intratracheally. Group HC received COX-2 inhibitor (celecoxib) 10 mg/kg intravenously 30 min before intratracheal instillation of HCl. Group C underwent bronchoalveolar lavage (BAL) only. All rats were mechanically ventilated for 30 min before BAL. Arterial blood gas analysis was done immediately before BAL. Groups H, S, and HC were subdivided to each two groups. Groups H-1, S-1, and HC-1 underwent BAL 1 h after instillation, whereas groups H-8, S-8, and HC-8 underwent BAL 8 h after instillation. The BAL fluid was used to measure the prostaglandin E2 (PGE2) concentration. Intratracheal HCl resulted in impaired oxygenation. COX-2 inhibitor attenuated the impairment of oxygenation 8 h after instillation but not after 1 h. Intratracheal HCl caused an increase in PGE2 concentration. COX-2 inhibitor attenuated an increase in PGE2 concentration 8 h after instillation but not after 1 h. The results show that COX-2 inhibitor attenuates the oxygenation impairment and the increase in alveolar PGE2 concentration during the inflammatory phase of acid aspiration-induced lung injury in rats.
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http://dx.doi.org/10.1007/s00540-005-0322-4 | DOI Listing |
Int J Mol Sci
January 2025
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland.
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January 2025
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, PR China. Electronic address:
A library comprising twenty-four isosteric derivatives of celecoxib substituted with carboxylic acid (labeled as 5a-5x), was synthesized and characterized through H NMR, C NMR, HRMS, and elemental analysis. Molecular docking studies revealed that all compounds successfully docked into the binding pocket of COX-2, and the introduction of carboxyl group enhances the interaction between the derivatives and COX-2. The compounds were further evaluated for cell toxicity, and in vitro anti-inflammatory activity.
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Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland;
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