Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis

Ramanpreet Kaur, Dhimant Desai, Shantu Amin, Kaisar Raza, Aman Bhalla, Pooja Yadav, Naveen Kaushal

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

Original languageEnglish (US)
Pages (from-to)621-636
Number of pages16
JournalMolecular and Cellular Biochemistry
Volume478
Issue number3
DOIs
StatePublished - Mar 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis'. Together they form a unique fingerprint.

Cite this