Detection of hypoxia in the mucosa. a) The in vivo evidence for hypoxia associated with inflammation (so called "inflammatory hypoxia") are provided using nitroimidazole-based dye retention in vitro and in mice. These molecules (R-NO2) are taken into cells passively and reduced to highly reactive nitrogen intermediates (R-NO2-[dot]). In the absence of adequate oxygen to regenerate the native compound, these intermediates react with cellular proteins to form adducts (R-NH2), which can be visualized using labeled antibodies. b) In the colons of mice with no inflammation (control) small amounts of nitroimidazole adduct is detected along the luminal aspect of the colon (red), suggesting a degree of physiological hypoxia in the normal colon. c) During episodes of inflammation, such as seen here in a mouse model of colitis, intense and deep tissue hypoxia is prevalent, particularly in areas overlying lesions.
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