The therapeutic effect of pristine C60 fullerene aqueous colloid solution (C60FAS) on the functioning of the rat soleus muscle at ischemic injury depending on the time of the general pathogenesis of muscular system and method of administration C60FAS in vivo was investigated. It was found that intravenous administration of C60FAS is the optimal for correction of speed macroparameters of contraction for ischemic muscle damage. At the same time, intramuscular administration of C60FAS shows pronounced protective effect in movements associated with the generation of maximum force responses or prolonged contractions, which increase the muscle fatigue level. Analysis of content concentration of creatine phosphokinase and lactate dehydrogenase enzymes in the blood of experimental animals indicates directly that C60FAS may be a promising therapeutic agent for the prevention and correction of ischemic-damaged skeletal muscle function.
The effect of C 60 fullerene nanoparticles (30-90 nm) on dynamics of force response development to stimulated soleus muscle of rat with ischemic pathology, existing in muscle during the first 5 hours and first 5 days after 2 hours of ischemia and further reperfusion, was investigated using the tensometric method. It was found that intravenous and intramuscular administration of С 60 fullerene with a single dose of 1 mg/kg exert different therapeutic effects dependent on the investigated macroparameters of muscle contraction. The intravenous drug administration was shown to be the most optimal for correction of the velocity macroparameters of contraction due to muscle tissue ischemic damage. In contrast, the intramuscular administration displays protective action with respect to motions associated with generation of maximal force response or continuous contractions elevating the level of muscle fatigue. Hence, С 60 fullerene, being a strong antioxidant, may be considered as a promising agent for effective therapy of pathological states of the muscle system caused by pathological action of free radical processes.
The self-organization of C60 fullerene and cisplatin in aqueous solution was investigated using the computer simulation, dynamic light scattering and atomic force microscopy techniques. The results evidence the complexation between the two compounds. The genotoxicity of С60 fullerene, Cis and their complex was evaluated in vitro with the comet assay using human resting lymphocytes and lymphocytes after blast transformation. The cytotoxicity of the mentioned compounds was estimated by Annexin V/PI double staining followed by flow cytometry. The results clearly demonstrate that water-soluble C60 fullerene nanoparticles (0.1 mg/mL) do not induce DNA strand breaks in normal and transformed cells. C60 fullerene in the mixture with Cis does not influence genotoxic Cis activity in vitro, affects the cell-death mode in treated resting human lymphocytes and reduces the fraction of necrotic cells.
The biomechanical parameters of muscle soleus contraction in rats and their blood biochemical indicators after the intramuscular administration of water-soluble C60 fullerene at doses of 0.5, 1, and 2 mg/kg 1 h before the onset of muscle ischemia were investigated. In particular, changes in the contraction force of the ischemic muscle soleus, the integrated power of the muscle, the time to achieve the maximum force response, the dynamics of fatigue processes, and the parameters of the transition from dentate to smooth tetanus, levels of creatinine, creatine kinase, lactate and lactate dehydrogenase, and parameters of prooxidant–antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, and reduced glutathione and catalase) were analyzed. The positive therapeutic changes in the studied biomechanical and biochemical markers were revealed, which indicate the possibility of using water-soluble C60 fullerenes as effective prophylactic nanoagents to reduce the severity of pathological conditions of the muscular system caused by ischemic damage to skeletal muscles.
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