Changes of AO status parameters and oxidative damages in cell structures are related to tumor processes indicating the augmentation of oxidative stress in human blood. This study demonstrated potential applicability of a statistical model based on the evaluated biomarkers of oxidative stress to determine a smoking-induced harm of cancer incidence in healthy subjects.
Probucol in concentrations of 10-50/aM effectively inhibits CuZ+-induced free radical oxidation of native low density lipoproteins and in concentration of 100 ~tM it inhibits lipoperoxide formation. The mean plasma concentration of probucol in patients receiving 250 mg of this drug is 25 ~tM. Both 250 and 1000 mg probucol daily during 3-6 month block the oxidation of isolated low density lipoproteins. Electron paramagnetic resonance spectrometry data showed that probucol incorporated in vivo into lipoprotein particles interacts with lipid radicals yielding long-lived phenoxyradicals. Probucol can be used in complex therapy of atherosclerosis as an antioxidant drug and its dose required for lipoprotein protection against atherogenic modification can be decreased to 250 mg/day.
Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism.
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