title: High selenium diet protects against TNBS-induced acute inflammation, mitochondrial dysfunction, and secondary necrosis in rat colon.
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.
  
  
  METHODS
  Rats were supplemented with sodium selenite for 21 d with a normal selenium diet (0.02 microg/g body weight), an intermediate selenium diet (ISD; 0.3 microg/g body weight), or a high selenium diet (HSD; 2 microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Tirosh
authors.forename: Eran
authors.initials: E
authors.lastname: Levy
authors.forename: Ram
authors.initials: R
authors.lastname: Reifen
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000008:administration & dosage* / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D004272:DNA, Mitochondrial; D014302:Trinitrobenzenesulfonic Acid; D012643:Selenium