Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Introduction Imaging of hypoxic areas Hypoxia markers Positron emission tomography (PET) Near-infrared spectroscopy (NIRS) Magnetic resonance spectroscopy (MRS) Electron paramagnetic resonance spectroscopy (EPR) Oxygen partial pressure measurement Polarographic sensor Optical sensor Mass spectrometry What does tumour hypoxia mean? Small molecules and hypoxia Chemotherapeutic drugs Radiation sensitizers: the nitroimidazoles Hypoxia prodrugs: tirapazimine and anthraquinone pO(2) modulator: myo-inositol trispyrophosphate (ITPP) Hypoxia mimetics: dimethyloxallyl glycine, desferrioxamine and metal ions What does physioxia mean? From air to blood In brain In lungs In skin In intestinal tissue In liver In kidney In muscle In bone marrow In umbilical cord blood To summarize physioxia Cellular and molecular consequences of physioxia versus normoxia and hypoxia Hypoxia inducible factors actions Role of microRNAs in hypoxia-dependent regulations Cell adhesion molecules: their regulation by oxygen partial pressure Soluble molecules: example of angiogenin Conclusion Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO(2)), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well-organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique 'tissue normoxia' or 'physioxia' status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO(2), i.e. 'hypoxia'. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO(2) values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O-2 whereas current in vitro experimentations are usually performed in 19.95% O-2, an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading.