ABSTRACT
It was studied the effect of doxorubicin on the HIF system and the pro-antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1α using doxorubicin at a dose of 0.5 µM was 2.9 ± 0.8 cu, so it decreased by 20% compared to control--3.6 ± 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50.4% relative to control. And after using doxorubicin and curcumin together, the percentage of dead cells decreased by 7,7 compared to doxorubicin only. Doxorubicin intoxication led to a significant increase in the secondary products of lipid peroxidation (TBARS) in cardiomyocytes by 3.6 times and hydrogen peroxide by 64%. Prolonged incubation with doxorubicin reduced the enzymatic activity of Mn-SOD by 32%, while catalase activity increased by 72% compared to control. Adding of curcumin to the cardiomyocyte cell culture contributed to increasing of the Mn-SOD activity by 14%, catalase--by 23%. The level of TBARS increased by 1,4 times compared with the control, and the level of H2O2 increased by 20%. The joint use of doxorubicin and curcumin resulted in a significant reduction of free radical oxidation unlike effect of doxorubicin per se. Specifically, there was lessening of TBARS and H2O2 (at 56.7 and 18.4% respectively), while decreasing of the catalase hyperactivation (19%) and rising of the Mn-SOD activity (35%).
Subject(s)
Antibiotics, Antineoplastic/toxicity , Antioxidants/pharmacology , Curcumin/pharmacology , Doxorubicin/toxicity , Myocytes, Cardiac/drug effects , RNA, Messenger/genetics , Animals , Animals, Newborn , Catalase/genetics , Catalase/metabolism , Doxorubicin/antagonists & inhibitors , Gene Expression Regulation , Glutathione/metabolism , Hydrogen Peroxide/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lipid Peroxidation , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Oxidative Stress/drug effects , Primary Cell Culture , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , RNA, Messenger/metabolism , Rats , Rats, Wistar , Signal Transduction , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The mechanisms of lipid peroxidation (LP) intensification in the rat myocardium, brain and liver were studied under hypoxic hypoxia and hemic hypoxia. The level of intensification depends on the type of hypoxia and is characterized by tissue specificity. It is shown that LP is activated by hypoxia. This activation is more pronounced under hemic hypoxia associated with more marked catecholamine accumulation, deficiency of the antioxidant glutathione system, decrease of the cytochrome c-oxidase activity. The level of lipid peroxides was higher in the rat liver under both types of hypoxia.
Subject(s)
Brain/physiology , Heart/physiology , Hypoxia/physiopathology , Lipid Peroxidation/physiology , Liver/physiology , Animals , Catecholamines/metabolism , Electron Transport Complex IV/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Male , Malondialdehyde/metabolism , Rats , Rats, WistarABSTRACT
It is shown that preliminary taurine treatment prevents the disturbances of energy metabolism in the brain, heart and liver tissues of Wistar rats with acute hypoxic hypoxia. Administration of taurine restored to normal the parameters of adenine pool: the concentration of ATP increased within the cytoplasm, while that of ADP and AMP diminished; mitochondrial respiration proceeded more rapidly; the concentrations of pyruvate and malate decreased; isocitrate dehydrogenase activity, P/O and NAD/NADH ratios increased. Taurine treatment resulted in a decreased level of lipid peroxides in the rat tissues with hypoxia. The role of intracellular calcium content and biomembranes structure changes as the mechanisms of taurine action on energy metabolism and lipid peroxidation is discussed.
