High selenium diet protects against TNBS-induced acute inflammation, mitochondrial dysfunction, and secondary...

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.

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.

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.

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.