ABSTRACT
The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body 60Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α1-adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT2 serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.
Subject(s)
Cystamine/pharmacology , Gamma Rays , Phenols/pharmacology , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/pharmacology , Adrenergic alpha-1 Receptor Antagonists/pharmacology , Animals , Aza Compounds/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cystamine/antagonists & inhibitors , Dose-Response Relationship, Radiation , Drug Administration Schedule , Female , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Phenols/antagonists & inhibitors , Prazosin/analogs & derivatives , Prazosin/pharmacology , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/pathology , Rats , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Serotonin, 5-HT2/metabolism , Reserpine/pharmacology , Whole-Body IrradiationABSTRACT
Female rats were exposed to local γ-irradiation of the right hindpaw in doses of 30-50 Gy at 131-154 sGy/min dose rate. Radioprotector indralin was administered per os 15 min prior to irradiation, monizol was injected intraperitoneally 5 min after irradiation. Indralin showed marked radioprotective properties both for acute and delayed symptoms of local radiation injuries. In combination with monizol, radioprotective effect of indralin was potentiated to dose reduction factor of 1.4-1.5 both for radiation burn severity reduction and for restriction of postradiational contracture development and amputation of the irradiated limb.
Subject(s)
Gamma Rays , Isosorbide Dinitrate/analogs & derivatives , Phenols/administration & dosage , Radiation Injuries, Experimental/drug therapy , Radiation-Protective Agents/administration & dosage , Skin Diseases/drug therapy , Acute Disease , Administration, Oral , Animals , Drug Therapy, Combination , Female , Injections, Intraperitoneal , Isosorbide Dinitrate/administration & dosage , Isosorbide Dinitrate/pharmacology , Phenols/pharmacology , Radiation Injuries, Experimental/pathology , Radiation-Protective Agents/pharmacology , Rats , Skin/pathology , Skin/radiation effects , Skin Diseases/etiology , Treatment OutcomeABSTRACT
This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.
Subject(s)
Betula , Genistein/pharmacology , Metal Nanoparticles , Phytotherapy , Plant Preparations/pharmacology , Radiation-Protective Agents/pharmacology , Animals , Animals, Outbred Strains , Betula/chemistry , Cholesterol Esters/chemistry , Drug Evaluation, Preclinical , Genistein/chemical synthesis , Genistein/chemistry , Genistein/toxicity , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mice , Particle Size , Pentacyclic Triterpenes/chemistry , Plant Bark/chemistry , Plant Preparations/chemical synthesis , Plant Preparations/chemistry , Plant Preparations/toxicity , Radiation Injuries, Experimental/drug therapy , Radiation-Protective Agents/chemical synthesis , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/toxicity , Random Allocation , Survival Analysis , Treatment Outcome , Triterpenes/chemistryABSTRACT
We studied the effect of long-term administration of melatonin to male C57Bl/6 mice starting from day 3 after whole-body γ-irradiation (9.5-10.0 Gy, 7.7-17.1 cGy/min). It was found that replacement of drinking water with melatonin solution (5 mg/liter) did not reduce the amount of fluid intake throughout the period of acute radiation injury. The daily dose of melatonin was 0.9-1.2 mg/kg body weight (this parameter was lower at the peak of the disease and increased during the recovery stage). Melatonin by more than 20% (p<0.05) improved survival of mice exposed to γ-irradiation in a dose of LD97/30, reduced leukopenia during the stage of acute manifestations of the disease and maximum mortality, and increased blood leukocyte count by 40% (p<0.05) by day 12 after irradiation.
Subject(s)
Acute Radiation Syndrome/drug therapy , Antioxidants/therapeutic use , Melatonin/therapeutic use , Radiation-Protective Agents/therapeutic use , Acute Radiation Syndrome/mortality , Animals , Gamma Rays/adverse effects , Leukocyte Count , Male , Mice , Mice, Inbred C57BL , Whole-Body Irradiation/adverse effectsABSTRACT
The effect of radioprotector indralin on the graft-versus-host reaction was studied on the model of acute GVH disease induced in mice by intraperitoneal transplantation of 40x10(6)semiallogenic splenocytes. The effect was evaluated by animal mortality from GVH disease. Recipients were male F1(CBAxC57Bl/6) mice exposed to 7 Gy 24 h before transplantation. Donors were male C57Bl/6 mice. Indralin, intraperitoneally injected in a dose of 100 mg/kg 5 min after irradiation attenuated the severity of GVH disease. It eliminated phase I of acute GVH reaction and shifted to the right the dynamics of mortality. Estimated time of 50% mortality (LT50) was prolonged by more than 4 days (the parameter increased by 31.1%). Two (5.7%) animals recovered from acute GVH disease, while all controls died. Indralin treatment after irradiation resulted in a 30% increase in survival of exposed mice.
Subject(s)
Graft vs Host Disease/drug therapy , Phenols/therapeutic use , Radiation-Protective Agents/therapeutic use , Animals , Cell Transplantation/adverse effects , Male , Mice , Mice, Inbred C57BL , Spleen/cytologyABSTRACT
A decrease in carboplatinum hemotoxicity was detected in experiments on C57B1 mice treated with the drug in combination with indralin (urgent radioprotector). Carboplatinum in a dose of 125 mg/kg, injected intraperitoneally, caused 80-100% death; the median term of death was 6 days (3-17). Single oral dose of indralin (100 mg/kg) during the 1st min or 15 min after carboplatinum injection (125 mg/kg) increased animal survival by 40.0-46.7% by day 20 of the experiment primarily during the period of manifest hemotoxicity (days 7-17), indralin injected 1, 2, or 4 h after carboplatinum exhibited no chemoprotective effect.
Subject(s)
Antineoplastic Agents/toxicity , Blood/drug effects , Blood/radiation effects , Carboplatin/toxicity , Phenols/administration & dosage , Phenols/pharmacology , Radiation-Protective Agents/pharmacology , Animals , Mice , Mice, Inbred C57BL , Radiation Injuries, Experimental/prevention & control , Time FactorsABSTRACT
Two compounds that deplete glutathione (buthionine sulfoximine and diethyl maleate) with different mechanisms of action decrease body temperature and increase tolerance to complete global cerebral ischemia, both correlating closely with the glutathione concentration decrease. Glutathione apparently participates in the regulations of these functional parameters. GSH diethyl ester does not influence the latter, though it increases moderately the GSH concentration. Injection of GSH ester into the cerebral ventricles or subcutaneously selectively increases the GSH level in the brain and liver. An influence of the brain on the glutathione system in the liver was revealed. Diethyl maleate and GSH ester increase the activity of glutathione metabolizing enzymes under certain conditions.
Subject(s)
Body Temperature , Brain Ischemia/metabolism , Glutathione/metabolism , Animals , Body Temperature/drug effects , Buthionine Sulfoximine/pharmacology , Dose-Response Relationship, Drug , Female , Injections, Intraventricular , Male , Mice , Monitoring, PhysiologicABSTRACT
Daily treatment of outbred albino mice with gammafos in radioprotective doses of 300 and 500 mg/kg for 4 days produced a cumulative toxic effect. This effect was not observed after decreasing the dose of gammafos to 100 mg/kg. Repeated peroral administration of melatonin and ascorbic acid in a dose of 200 mg/kg 30 min before treatment with gammafos reduced its cumulative toxic effect. Succinic acid in a dose of 100 mg/kg was ineffective under these conditions. The cumulative death time for 50% animals receiving gammafos alone or in combination with melatonin, ascorbic acid, and succinic acid was 3.08, 4.29, 4.06, and 2.97 days, respectively.