ABSTRACT
A new class of substances exhibiting radioprotective and radiosensitizing effects depending on the concentration of the substance has been found. The radioprotective effect is probably due to the resonant absorption of radiation energy and its transformation into low-energy forms, as well as reactions with water radiolysis products. We studied the effects of 2,5-difeniloxazole and di[2-(5-feniloxazolil)]benzene in various concentrations in conjunction with irradiation on the growth of melanoma B-16 in mice and the average time of their lives. When using individual doses of irradiation and doses of preparations, we observed an increase in the average lifetime of mice and a reduced tumor size. These data allow us to conclude about the possibility of using these substances in the radiotherapy of tumors.
Subject(s)
Benzene Derivatives/pharmacology , DNA/drug effects , Oxazoles/pharmacology , Radiation-Protective Agents/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Benzene Derivatives/chemistry , Cell Membrane/drug effects , Cell Membrane/radiation effects , DNA/radiation effects , DNA Breaks, Double-Stranded/drug effects , Dose-Response Relationship, Radiation , Melanoma, Experimental , Mice , Mice, Inbred BALB C , Oxazoles/chemistry , Radiation-Protective Agents/chemistry , Radiation-Sensitizing Agents/chemistry , Spleen/cytology , Spleen/drug effects , Spleen/radiation effects , Water/chemistry , Whole-Body IrradiationABSTRACT
The dependence of "biological effect-dose" in experiments on mature outbreed mice (females) is studied during 30 days after low intensity X-ray action at the total dose less than 1 mGy. The index (relative mass) of the murine spleen was decreased in the group of mice which have the low value of the spleen index in the control. It is shown that the value of these parameters in groups of irradiated mice is mainly due to the total X-ray doses. The content of the lipid peroxidation products and the amount of the extracellular DNA in blood plasma of the irradiated mice are mainly determined by the change of dose rate during irradiation. The absence of linear interrelation between changes of all studied parameters and the total radiation dose is revealed. The data obtained allow us to suggest the relative mass of the murine spleen, the content of the lipid peroxidation products and the amount of the extracellular DNA as a test for estimation of the biological consequences of X-ray radiation at low doses and changing dose rate.
Subject(s)
Radiation Injuries, Experimental/blood , Spleen/radiation effects , X-Rays/adverse effects , Animals , Biomarkers/blood , DNA/blood , DNA/radiation effects , Dose-Response Relationship, Radiation , Female , Lipid Metabolism/radiation effects , Lipids/blood , Mice , Organ Size/radiation effects , Radiation Injuries, Experimental/pathology , Spleen/pathology , Whole-Body IrradiationABSTRACT
Synthetic antioxidant potassium phenosan in ultralow doses administrated in combination with antitumor antibiotic adriamycin in a therapeutic dose (8 mg/kg) markedly prolonged the mean life span of tumor-bearing animals compared to adriamycin monotherapy. This effect depended on the dose of antioxidant and was maximum at phenosan concentrations of 10(-17) and 10(-15) M. Potassium phenosan in these concentrations not only increased the mean life span, but also determined survival of 10-20% animals (as differentiated from adriamycin monotherapy).
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antioxidants/therapeutic use , Leukemia/drug therapy , Animals , Doxorubicin/therapeutic use , Drug Interactions , Mice , Mice, Inbred C57BL , Phenothiazines/therapeutic useABSTRACT
On the basis of antioxidant (alpha-tocopherol and phenosan potassium salt) and peptide (thyroliberin) effects on the lipid peroxide oxidation (LPO) and lipid structural parameters of the endoplasmic reticulum membranes in wide concentration range (10(-20)-10(-4) mol/l) in vitro the possibility concerning a proposed role of "super-affine" receptors in the mechanism of biologically active substances (BAS) action in ultra low doses (ULD) is discussed. Because these substances modulate investigated processes in the membranes which have not ordinarily receptors the conclusion about availability of non-receptor component in the mechanism of BAS effect in ULD and a low probability of "super-affine" receptor existence has been done.
Subject(s)
Antioxidants/pharmacology , Endoplasmic Reticulum/drug effects , Lipid Peroxidation/drug effects , Phenylpropionates/pharmacology , alpha-Tocopherol/pharmacology , Animals , Dose-Response Relationship, Drug , Endoplasmic Reticulum/chemistry , Endoplasmic Reticulum/metabolism , Intracellular Membranes/chemistry , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Kinetics , Lipid Bilayers , Liver/cytology , Liver/drug effects , Malondialdehyde/analysis , Malondialdehyde/metabolism , Mice , Thyrotropin-Releasing Hormone/pharmacology , ViscosityABSTRACT
Acetylcholinesterase (ACE) activity and lipid peroxidation (LPO) parameters were measured in the blood of patients with Alzheimer's disease (AD) during treatment with amiridine and gliatiline. Treatment was accompanied by inhibition of ACE. There was a statistically significant relationship between clinical efficacy and changes in ACE activity. AD was charactefized by significant changes in LPO parameters, with a three-fold increase in the level of primary oxidation products on the background of a sharp (seven-fold) increase in total lipid desaturatedness. There was a statistically significant relationship between ACE activity and the levels of primary oxidation products in the RBC of patients with AD before and after treatment with amiridine and gliatiline.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/drug therapy , Aminoquinolines , Cholinergic Agents/therapeutic use , Acetylcholinesterase/blood , Aged , Butyrylcholinesterase/blood , Cholinesterase Inhibitors/therapeutic use , Erythrocytes/drug effects , Erythrocytes/enzymology , Female , Humans , Lipid Peroxidation/drug effects , Male , Middle Aged , Neurodegenerative Diseases/blood , Neurodegenerative Diseases/enzymology , Neuroprotective Agents/therapeutic useABSTRACT
Acetylcholinesterase (AChE) activity and parameters of the system of regulation of lipid peroxidation (LPO) were estimated in blood of patients with Alzheimer's disease (AD) during therapy with amiridine and gliatiline. It was found that the therapy was accompanied by inhibition of AChE activity. A significant correlation was observed between clinical efficiency and changes of AChE activity. AD was characterised by essential changes in LPO parameters: the level of the primary products of oxidation was increased three times with a sharp increase (seven times) of total unsaturation of lipids. A significant correlation was found between AChE activity and the level of the primary products of oxidation in blood erythrocytes of AD patients before and after therapy with amiridine and gliatiline.
Subject(s)
Alzheimer Disease/drug therapy , Aminoquinolines , Cholinesterase Inhibitors/therapeutic use , Neuroprotective Agents/therapeutic use , Aged , Cognition Disorders/diagnosis , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Severity of Illness IndexSubject(s)
Antioxidants/pharmacology , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Viral , Oxidative Stress , Animals , Cell Line, Transformed , Cell Transformation, Neoplastic/drug effects , Cell Transformation, Viral/drug effects , Cricetinae , Mesocricetus , Oncogene Protein pp60(v-src)/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
The phospholipid composition and the antioxidative activity (AOA) of lipids from liver, heart and brain of F1(CBA X C57Bl) mice change significantly after intraperitoneal injection of adriamycin (7 mg/kg). All tissues studied are characterized by a drastic fall in the phosphatidylethanolamine (PEA) content and the AOA of lipids with a minimum on the 2nd-4th days and a subsequent return to normal values on the 10th-14th days. These results are consistent with the hypothesis on the intensification of adriamycin-induced lipid peroxidation and the predominant expenditure of readily oxidized phospholipids, including PEA.
Subject(s)
Doxorubicin/pharmacology , Lipid Metabolism , Phospholipids/analysis , Animals , Brain/metabolism , Liver/metabolism , Mice , Mice, Inbred Strains , Myocardium/metabolism , Organ Specificity , Oxidation-Reduction , Phosphatidylethanolamines/metabolismABSTRACT
Based on studies of the antioxidative activity of lipids (aoa) of the organs and tissues of tumor-bearing animals during tumor growth, it is suggested to use the following schedule of combined chemotherapy of tumors: at early terms of tumor progression, when the level of aoa in the organs of a tumor-bearing animal is maximum, to inject alkylating agents which sharply reduce the aoa level, when their level in tissue is low to inject synthetic antioxidants which raise it.
