Protective Effect of Water-Soluble C60 Fullerene Nanoparticles on the Ischemia-Reperfusion Injury of the Muscle Soleus in Rats.

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.

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene.

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 µg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40-45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55-65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.

С60 fullerene protective effect against the rat muscle soleus trauma.

Muscle trauma is one of the most common body injuries. Severe consequences of muscle trauma are ischemic injuries of the extremities. It is known that the intensification of free radical processes takes place in almost most acute diseases and conditions, including muscle trauma. C60 fullerene (C60) with powerful antioxidant properties can be considered a potential nanoagent for developing an effective therapy for skeletal muscle trauma. Here the water-soluble C60 was prepared and its structural organization has been studied by the atomic force microscopy and dynamic light scattering techniques. The selective biomechanical parameters of muscle soleus contraction and biochemical indicators of blood in rats were evaluated after intramuscular injection of C60 1 h before the muscle trauma initiation. Analysis of the force muscle response after C60 injection (1 mg kg-1 dose) showed its protective effect against ischemia and mechanical injury at the level of 30 ± 2 % and 17 ± 1 %, accordingly, relative to the pathology group. Analysis of biomechanical parameters that are responsible for correcting precise positioning confirmed the effectiveness of C60 at a level of more than 50 ± 3 % relative to the pathology group. Moreover, a decrease in the biochemical indicators of blood by about 33 ± 2 % and 10 ± 1 % in ischemia and mechanical injury, correspondingly, relative to the pathology group occurs. The results obtained demonstrate the ability of C60 to correct the functional activity of damaged skeletal muscle.

Effect of C60 Fullerene on Muscle Injury-Induced Rhabdomyolysis and Associated Acute Renal Failure.

Introduction: Rhabdomyolysis, as an acute stage of myopathy, causes kidney damage. It is known that this pathology is caused by the accumulation of muscle breakdown products and is associated with oxidative stress. Therefore, the present study evaluated the effect of intraperitoneal administration (dose 1 mg/kg) of water-soluble C60 fullerenes, as powerful antioxidants, on the development of rat kidney damage due to rhabdomyolysis caused by mechanical trauma of the muscle soleus of different severity (crush syndrome lasting 1 min under a pressure of 2.5, 3.5, and 4.5 kg/cm2, respectively). Methods: Using tensometry, biochemical and histopathological analyses, the biomechanical parameters of muscle soleus contraction (contraction force and integrated muscle power), biochemical indicators of rat blood (concentrations of creatinine, creatine phosphokinase, urea and hydrogen peroxide, catalase and superoxide dismutase activity), glomerular filtration rate and fractional sodium excretion value, as well as pathohistological and morphometric features of muscle and kidney damages in rats on days 1, 3, 6 and 9 after the initiation of the injury were studied. Results: Positive changes in biomechanical and biochemical parameters were found during the experiment by about 27-30 ± 2%, as well as a decrease in pathohistological and morphometric features of muscle and kidney damages in rats treated with water-soluble C60 fullerenes. Conclusion: These findings indicate the potential application of water-soluble C60 fullerenes in the treatment of pathological conditions of the muscular system caused by rhabdomyolysis and the associated oxidative stress.

Effect of C60 Fullerene on Recovery of Muscle Soleus in Rats after Atrophy Induced by Achillotenotomy.

Biomechanical and biochemical changes in the muscle soleus of rats during imitation of hind limbs unuse were studied in the model of the Achilles tendon rupture (Achillotenotomy). Oral administration of water-soluble C60 fullerene at a dose of 1 mg/kg was used as a therapeutic agent throughout the experiment. Changes in the force of contraction and the integrated power of the muscle, the time to reach the maximum force response, the mechanics of fatigue processes development, in particular, the transition from dentate to smooth tetanus, as well as the levels of pro- and antioxidant balance in the blood of rats on days 15, 30 and 45 after injury were described. The obtained results indicate a promising prospect for C60 fullerene use as a powerful antioxidant for reducing and correcting pathological conditions of the muscular system arising from skeletal muscle atrophy.

Analysis of Biomechanical and Biochemical Markers of Rat Muscle Soleus Fatigue Processes Development during Long-Term Use of C60 Fullerene and N-Acetylcysteine.

The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C60 fullerene, as a powerful antioxidant, is very attractive. In this study, a comparative analysis of the dynamic of muscle soleus fatigue processes in rats was conducted using 50 Hz stimulation for 5 s with three consistent pools after intraperitoneal administration of the following antioxidants: C60 fullerene (a daily dose of 1 mg/kg one hour prior to the start of the experiment) and N-acetylcysteine (NAC; a daily dose of 150 mg/kg one hour prior to the start of the experiment) during five days. Changes in the integrated power of muscle contraction, levels of the maximum and minimum contraction force generation, time of reduction of the contraction force by 50% of its maximum value, achievement of the maximum force response, and delay of the beginning of a single contraction force response were analyzed as biomechanical markers of fatigue processes. Levels of creatinine, creatine phosphokinase, lactate, and lactate dehydrogenase, as well as pro- and antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione, and catalase activity) in the blood of rats were analyzed as biochemical markers of fatigue processes. The obtained data indicate that applied therapeutic drugs have the most significant effects on the 2nd and especially the 3rd stimulation pools. Thus, the application of C60 fullerene has a (50-80)% stronger effect on the resumption of muscle biomechanics after the beginning of fatigue than NAC on the first day of the experiment. There is a clear trend toward a positive change in all studied biochemical parameters by about (12-15)% after therapeutic administration of NAC and by (20-25)% after using C60 fullerene throughout the experiment. These findings demonstrate the promise of using C60 fullerenes as potential therapeutic nanoagents that can reduce or adjust the pathological conditions of the muscular system that occur during fatigue processes in skeletal muscles.

Increased myofiber remodelling and NFATc1-myonuclear translocation in rat postural skeletal muscle after experimental vestibular deafferentation.

BACKGROUND: The vestibular system undergoes considerable modification during spaceflight [5]. This is paralleled by microgravity-induced muscle atrophy [6]. However, the possibility of vestibulo-autonomic regulatory mechanisms affecting skeletal muscle structure and function have not yet been addressed. OBJECTIVE: We hypothesise that the vestibular system affects anti-gravitational skeletal muscle phenotype composition, size and the transcriptional factor called nuclear factor of activated T cells (NFATc1). METHODS: In a laboratory study, we examined the morphological and histochemical properties including intramyocellular NFATc1 changes in slow-type soleus muscle of chemically labyrinthectomized rats (VLx; n=8) compared to a control group (Sham; n=6) after a period of one month. RESULTS AND CONCLUSION: Neurochemical vestibular deafferentation resulted in smaller myofibre sizes, altered myofibre phenotype composition, high yields of hybrid fibre formation, and reduced myonuclear NFATc1 accumulation as signs of slow-type myofibre atrophy, myofibre type remodelling, and altered nuclear transcriptional activity in the postural soleus muscle of rats. We propose that vestibulo-autonomic modification of skeletal muscles occurs during prolonged microgravity. Our findings are likely to have implications for vestibular rehabilitation in clinical settings.