TY - JOUR
T1 - High selenium diet protects against TNBS-induced acute inflammation, mitochondrial dysfunction, and secondary necrosis in rat colon
AU - Tirosh, Oren
AU - Levy, Eran
AU - Reifen, Ram
N1 - Funding Information:
This work was supported in part by a research grant from the Israel Ministry of Health to Ram Reifen and Oren Tirosh.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - Colitis
KW - Inflammation
KW - Mitochondria
KW - Necrosis
KW - Selenium
UR - http://www.scopus.com/inward/record.url?scp=35148823272&partnerID=8YFLogxK
U2 - 10.1016/j.nut.2007.08.019
DO - 10.1016/j.nut.2007.08.019
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C2 - 17936198
AN - SCOPUS:35148823272
SN - 0899-9007
VL - 23
SP - 878
EP - 886
JO - Nutrition
JF - Nutrition
IS - 11-12
ER -