Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation

Abstract

Radiotherapy is considered as a primary modality for cancer treatment which accompanied by several side effects. Protection of normal tissues from radiation effects is one of the most significant concerns for researchers. Although many compounds acting as radio protectors, only two compounds were licensed clinically. Cyclooxygenase-2 (COX-2), as an inflammatory mediator is associated with ROS production with a NF-κB gene up regulation dependent manner in normal tissues. To that extend, his study was designed to target COX-2 and NF-κB by a newly synthesized benzopyran-4-one or chromone derivative; (2E)-2-((4-oxo-4H-chromen-3-yl) methylene amino-4- nitrobenzoic acid (Ch). Exposure of mice to IRR significantly induced intestinal inflammation via overexpression of COX-2 and NF-κB which is accompanied by an increase in the levels of MDA and iNOS in tissue homogenate and in the production of TNF-α and IL-6 as inflammatory signs. Moreover, the apoptotic effect of IRR was manifested by obvious elevation in caspase-3. Interapretonial injection of Ch significantly controls the inflammatory response by blocking the COX-2 and decrease the expression NF-κB which subsequently decreases other inflammatory parameters. Thus Ch compound might be a promising nonsteroidal anti-inflammatory drug (NSAID) against radiation-induced inflammation with a specific mode of COX-2 inhibition. Further researches are needed to elucidate its molecular mechanism and its combination with radiotherapy as a protector.