Relation between colonic inflammation severity and total low-molecular- weight antioxidant profiles in experimental colitis

Sigal Blau, Ron Kohen, Paul Bass, Abraham Rubinstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Tissue antioxidant status is altered as a response to oxidative stress. This oxidative stress, caused by reactive oxygen species, is associated with inflammatory bowel disease (IBD). Our aim was to examine the relationship between total tissue low-molecular-weight antioxidant (LMWA) profile and inflammation severity in dinitrobenzene sulfonic acid (DNBS) experimental colitis in the rat. Rats were treated with three doses of DNBS: 1, 10, and 20 mg. Inflammation severity was assessed by tissue colonic wet weight, macroscopic evaluation, and tissue myeloperoxidase (MPO) activity. The capacity of water-soluble LMWA was assessed by measuring the reducing power of the tissues with cyclic voltammetry (CV) and by measuring tissue levels of reduced glutathione. While typical markers of inflammation (MPO, macroscopic examination, and colonic wet weight) indicated DNBS dose dependency, such dependency could not be demonstrated for the tissue LMWA as measured by reduced glutathione levels and by the tissues' reducing power. Mild colonic inflammation (induced by ethanol or by 1 mg Of DNBS) caused an increase in the overall capacity of water-soluble LMWA. However, severe inflammation (induced by 20 mg of DNBS) caused a reduction in the tissue LMWA capacity. An intermediate dose of DNBS (10 mg) caused moderate inflammation, but did not cause a significant change in the tissue LMWA compared with a saline control treatment. In conclusion, LMWA changed in a biphasic pattern reflective of the severity of mucosal colonic inflammation. It is suggested that: low dose of DNBS (1 mg) and topical alcohol (25% v/v) caused an adaptation effect to the mild oxidative Stress associated with mild inflammation. This resulted in an increase in the LMWA. A higher dose of DNBS (20 mg) caused more severe inflammation with an overall reduction in LMWA. The increased efflux of reactive oxygen species, associated with severe inflammation, led to an overall consumption of the tissue LMWA, which masked the increase in LMWA caused by the mild oxidative stress.

Original languageAmerican English
Pages (from-to)1180-1187
Number of pages8
JournalDigestive Diseases and Sciences
Volume45
Issue number6
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
The study was supported by research grant number 93-56 from the American-Israeli Binational Foundation. The results reported here are included in the dissertation project of S.B. as partial fulfillment of her PhD degree requirements at The Hebrew University of Jerusalem.

Keywords

  • Cyclic voltammetry
  • Dinitrobenzene sulfonic-acid
  • Experimental colitis
  • Glutathione
  • Low-molecular-weight antioxidants
  • Oxidative stress

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