Abstract
Objective: We studied the protective effects of selenium in a rat model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis to elucidate a possible mechanism of action. Method: Rats were supplemented with sodium selenite for 21 d with a normal selenium diet (0.02 μg/g body weight), an intermediate selenium diet (ISD; 0.3 μg/g body weight), or a high selenium diet (HSD; 2 μg/g body weight). On day 22, colitis was induced with TNBS. Rats were sacrificed after 24 h and colonic tissue was removed for evaluation. Results: Selenium supplementation (HSD) resulted in a significant increase in selenium in colonic tissue. Morphologically, the HSD resulted in the preservation of tissue architecture and attenuated neutrophil infiltration; no vasculitis or necrosis was detected. Biochemically, the HSD decreased tissue myeloperoxidase activity and protected the mitochondria in the colon of TNBS-treated animals as evaluated by preserving tissue oxygen consumption, mitochondrial DNA, and expression of cytochrome c. The HSD increased levels of nuclear respiratory factor-1 and mitochondrial transcription factor-A in normal colon tissue and under inflammatory conditions. The ISD resulted in only a minor protective effect. Conclusion: The results indicate that tissue damage in TNBS-induced colitis is accompanied by the arrest of mitochondrial respiration, loss of mitochondrial DNA, and the expression of nuclear-encoded mitochondrial proteins. Selenium effectively protects colon mitochondria by upregulation of the expression of mitochondrial transcription factors nuclear respiratory factor-1 and mitochondrial transcription factor-A. Selenium prevented inflammatory and necrotic changes after induction of colitis. Selenium in a high dose is therefore a potential therapeutic agent in inflammatory bowel disease.
Original language | American English |
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Pages (from-to) | 878-886 |
Number of pages | 9 |
Journal | Nutrition |
Volume | 23 |
Issue number | 11-12 |
DOIs | |
State | Published - Nov 2007 |
Bibliographical note
Funding Information:This work was supported in part by a research grant from the Israel Ministry of Health to Ram Reifen and Oren Tirosh.
Keywords
- Colitis
- Inflammation
- Mitochondria
- Necrosis
- Selenium