Alterations in Red Blood Cells and Plasma Properties after Acute Single Bout of Exercise

The aim of this study was to investigate alterations in haemoglobin conformation and parameters related to oxidative stress in whole erythrocytes, membranes, and plasma after a single bout of exercise in a group of young untrained men. Venous blood samples from eleven healthy young untrained males (age = 22 ± 2 years, BMI = 23 ± 2.5 kg/m2) were taken from the antecubital vein before an incremental cycling exercise test, immediately after exercise, and 1 hour after exercise. Individual heart rate response to this exercise was 195 ± 12 beats/min and the maximum wattage was 292 ± 27 W. Immediately after exercise, significant increase in standard parameters (haemoglobin, haematocrit, lactate levels, and plasma volume) of blood was observed as well as plasma antioxidant capacity one hour after exercise. Reversible conformational changes in haemoglobin, measured using a maleimide spin label, were found immediately following exercise. The concentration of ascorbic acid inside erythrocytes significantly decreased after exercise. A significant decline in membrane thiols was observed one hour after exercise, but simultaneously an increase in plasma thiols immediately after and 1 h after exercise was also observed. This study shows that a single bout of exercise can lead to mobilization of defensive antioxidant systems in blood against oxidative stress in young untrained men

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Combination of doxorubicin (DOX) and docetaxel (DTX) is clinically effective against many drug-refractory cancers, nevertheless, enhanced side effects, e.g. cardiotoxicity related to oxidative damage of tissue macromolecules is observed. Nitroxides represent an attractive class of synthetic compounds to ameliorate DOX-DTX toxicity in nontargeted tissues due to their antioxidant and iron-oxidizing properties. The aim of the study was to define the ability of 3-carbamoylpyrroline nitroxyl derivative pirolin (PL) to mitigate oxidative damage to blood plasma proteins and lipids induced by DOX-DTX chemotherapy in Sprague-Dawley rats bearing DMBA-induced mammary tumor. Additionally we also evaluated: i) pro-oxidant and antioxidant activity of pirolin administered as a single agent according to different regimens and ii) differences in biomarkers of the oxidative stress between healthy rats and rats with DMBA-induced mammary tumors. The extent of oxidative stress was evaluated on the basis of its foremost biomarkers: thiol and carbonyl groups, lipid peroxidation products (hydroperoxides, TBARS), activity of antioxidant defense enzyme superoxide dismutase (SOD) and non-enzymatic antioxidant capacity (NEAC). We have found that pirolin alone displayed dual, antioxidant and pro-oxidant activity depending on the regimen of treatment. Daily treatment for 2 weeks increased the amount of thiols, and decreased the protein carbonyl groups. Three administrations of pirolin at 3-week intervals did not influence thiol content but increased hydroperoxides, TBARS and carbonyl groups. Chemotherapy employing DOX-DTX combination caused considerable oxidative stress in the plasma. Significant and dose-dependent oxidative damage to lipids and proteins with concomitant thiol depletion were evident in treated animals. Drugs also increased SOD activity and NEAC. Association of pirolin with DOX-DTX chemotherapy resulted in a partial amelioration of oxidative stress generated by anticancer drugs. This study indicates that a nitroxyl compound pirolin applied as a single agent in vivo can display both antioxidant and pro-oxidant properties but in conjunction with DOX-DTX it is able to protect partially blood plasma against oxidative stress generated by chemotherapy. The outcome, however, seems to be highly dependent on the ratio between the doses of employed anticancer drugs and the nitroxide. K e y w o r d s : chemotherapy, docetaxel, doxorubicin, nitroxide, pirolin, oxidative stress, superoxide dismutase, reactive oxygen specie