期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 47, 期 5, 页码 510-517出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.05.015
关键词
Ischemia-reperfusion; Nitrite; Diet; Gene expression; Free radicals
资金
- National Heart, Lung, and Blood Institute
- Critical Care Medicine Department at the Clinical Center
- Intramural Research Program at the National Institutes of Health
- U.S. government
- U.S. government Collaborative Research and Development Agreement with INO-Ikaria
Dietary nitrate,found in abundance in green vegetables, can be converted to the cytoprotective molecule nitrite by oral bacteria, suggesting that nitrate and nitrite may represent active cardioprotective constituents of the Mediterranean diet. We therefore tested the hypothesis that dietary nitrate and nitrite levels modulate tissue damage and ischemic gene expression in a mouse liver ischemia-reperfusion model. We found that stomach content, plasma, heart, and liver nitrite levels were significantly reduced after dietary nitrate and nitrite depletion and could be restored to normal levels with nitrite supplementation in water. Remarkably, we confirmed that basal nitrite levels significantly reduced liver injury after ischemia-reperfusion. Consistent with an effect of nitrite on the posttranslational modification of complex I of the mitochondrial electron transport chain, the severity of liver infarction was inversely proportional to complex I activity after nitrite repletion in the diet. The transcriptional response of dietary nitrite after ischemia was more robust than after normoxia, suggesting a hypoxic potentiation of nitrite-dependent transcriptional signaling. Our studies indicate that normal dietary nitrate and nitrite levels modulate ischemic stress responses and hypoxic gene expression programs, supporting the hypothesis that dietary nitrate and nitrite are cytoprotective components of the diet. (C) 2009 Elsevier Inc. All rights reserved.
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