Role of oxidative stress in mediating intestinal iNOS expression
2008
Markovs, J., University of Latvia, Riga (Latvia). Faculty of Medicine | Berzina, N., University of Latvia, Salaspils (Latvia). Inst. of Biology | Svirina, D., University of Latvia, Riga (Latvia). Faculty of Medicine | Isajevs, S., University of Latvia, Riga (Latvia). Faculty of Medicine | Knipse, G., University of Latvia, Riga (Latvia). Faculty of Medicine
This study investigated changes in the expression pattern of iNOS (inducible nitric oxide synthase) as well as morphological changes in the intestinal wall during chicken exposure to excess of ascorbic acid. In control animals, iNOS expression has been identified primarily in villus enterocyte brush border, as well as in enteroendocrine cells, in mucosal macrophages and in myenteric neurons. In chicken intestinal mucosa during high-dose ascorbic acid administration the level of oxidative stress marker - malondialdehyde was increased. Oxidative stress upregulates iNOS expression by apoptotic enterocytes. This indicates that NO acts as a mediator of apoptosis. The subchronic ascorbic acid treatment caused an increase in the number of IEL and mucosal macrophages highly expressing NF-kB and iNOS. These results show that the excess ascorbic acid can upregulate the expression of iNOS in intestinal mucosa and suggest that this regulation is probably mediated by oxidative stress-induced NF-kB activation. There would be a high probability that excess nitric oxide alters neuroendocrine signaling in the small intestine during long-term oxidative stress. The results reported here reveal a tight relationship between oxidative stress and compensatory upregulation of iNOS in the gut mucosa, thus enhancing reactive nitrogen species generation and apoptosis.
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