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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.

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.

The protective effect of water-soluble C60 fullerenes on the development of slow and rapid fatigue of rat skeletal muscles was analyzed. It was found that the reduction of muscle contraction force (muscle soleus) by 50% of the initial values is almost twice as slow as stimulation with a frequency of 1 Hz (slow muscle fatigue) than with 2 Hz (rapid muscle fatigue) stimulation after intramuscular injection of C60 fullerenes (dose 0.5 mg/kg). There is a clear tendency to decrease the values of biochemical parameters of the blood of animals with the therapeutic effect of water-soluble C60 fullerenes by approximately 45-60% and 35-40% with the development of slow and rapid muscle fatigue, respectively. Thus, C60 fullerenes, as powerful antioxidants, are able to efficiently affect the prooxidant-antioxidant homeostasis of muscle tissue and thus help maintain its normal physiological state.

Досліджено зміни рівня запалення у травмованого muscle soleus щурів при використанні таких терапевтичних аґентів, як C60-фуллерен (доза — 1 мг/кг), ментол (доза — 1 мг/кг), та їхнього спільного застосування у вигляді внутрішньом’язових ін’єкцій. Як біомеханічний маркер запального процесу в м’язі проаналізовано зміну його жорсткости. Досліджено зміни про- й антиоксидантного балансу в крові щурів після індукування м’язової травми та застосованих терапевтичних аґентів, а саме, концентрації ТБК-активних продуктів перекисного окиснення ліпідів, перекису водню, відновленого глутатіону й активности каталази (ТБК — тіобарбітурова кислота). Встановлено значну синерґетичну дію C60-фуллерена та ментолу на запальний процес у травмованому м’язі, що відкриває можливість комбінованого застосування їх як ефективних терапевтичних аґентів.

Rhabdomyolysis, as an acute stage of myopathy is known to be associated with the accumulation of muscle breakdown products, acute renal failure and oxidative stress. The goal of the study was to evaluate the effect of C60 fullerene as an antioxidant on kidney damage in the model of glycerol-induced rhabdomyolysis in rats. The study was conducted on male Wistar rats, divided into the following experimental groups: control animals, animals intramuscularly injected with glycerol in a doses of 5, 10 and 15 mg/kg and those intraperitoneally injected daily with C60 fullerene aqueous solution (C60FAS) in a dose of 1 or 2 mg/kg at 48 h after glycerol administration­. Monitoring of the biochemical and morphological indicators was carried out on 3rd, 6th and 9th days of the experiment. A close correlation between the acute renal damage severity, increased creatinine and urea level, superoxide dismutase (SOD) and catalase (CAT) activity in the blood of rats was observed. It was shown that in rats which received 2 mg/kg of C60FAS the renal glomeruli size and necrosis manifestations were attenuated, whereas SOD and CAT activity in the blood was significantly decreased. The results obtained may be useful for developing approaches to the treatment of pathological conditions of the muscular system caused by rhabdomyolysis and associated oxidative stress. Keywords: acute renal failure, biochemical parameters, C60 fullerene, histopathology, muscle soleus, rhabdomyolysis.

Background. The search for new means that would effectively influence the pathological consequences of muscle immobilization is an urgent priority request of modern biomedicine. Previously, the positive effect of water-soluble C60 fullerenes, as strong antioxidants, was established on the background of muscle ischemia, mechanical muscle injury, and other muscle dysfunctions. These carbon nanoparticles have been shown to reliably protect muscle tissue from damage caused by oxidative stress. Materials and Methods. The biomechanical parameters of muscle soleus contraction of rats were studied by simulating non-functioning hind limbs using a clinical model – a rupture of the Achilles tendon (achillotomy). Muscle contraction parameters, namely the maximum contraction force and muscle force impulse, were determined on the 15th, 30th, and 45th days after initiation of atrophy using tensometry. As a therapeutic nanoagent, daily oral administration of C60 fullerene aqueous solution at a dose of 1 mg/kg was used throughout the experiment. Results. Previous registration of muscle soleus contraction force when applying 1 Hz stimulation lasting 1800 s with three pools revealed a decrease in maximal force responses after 15, 30, and 45 days of atrophy. The 45th day after atrophy is considered to be the limit for the fastest recovery of the muscle after immobilization, the further process takes place over several months. In all the tests performed, the therapeutic admini­stration of water-soluble C60 fullerenes (dose 1 mg/kg) an increase in biomechanical parameters was recorded (maximum force of contraction – the change in the form of the “stimulation – force contraction” dependence is a consequence of the development of the pathological process in muscle and the muscle force impulse, which allows assessing the performance of the muscular system after a long-term immobilization), by approximately 29–49±2 % for the maximum contraction force and by 21–37±2 % for the muscle force impulse compared to the atrophy group for 15, 30 and 45 days. Conclusions. The obtained results indicate the prospects of using water-soluble C60 fullerenes, which can alleviate pathological conditions in the muscular system that arise from skeletal muscle atrophy due to immobilization.

Traumatic skeletal muscle injury is a complex pathology caused by high-energy trauma to muscle tissue. Previously, a positive effect was established when C60 fullerene was administered against the background of muscle ischemia, mechanical muscle injury, and other muscle dysfunctions, which probably protected the muscle tissue from damage caused by oxidative stress. Using tensiometry and biochemical analysis, the biomechanical parameters of skeletal muscle contraction and biochemical indices of the blood of rats 15 days after traumatic injury of the soleus muscle caused by myocyte destruction by compression were studied. The intraperitoneal administration of C60 fullerene aqueous solution (C60FAS) in a daily dose of 1 mg/kg improved its contractile function by 28–40 ± 2% and the values of the investigated biochemical indices of the animals’ blood by 15–34 ± 2% relative to the trauma group. The obtained results indicate the potential ability of C60 fullerenes, as powerful antioxidants, to reduce the development of post-traumatic dysfunction of the soleus muscle.

The powerful antioxidant properties of C60 fullerenes have been widely used in biomedical nanotechnology. Owing to the negative effects of free radicals in oxidative stress processes, antioxidants are required to protect injured muscles. Here, the effect of water-soluble C60 fullerenes (daily oral dose 1 mg kg−1) on the process of restoration of contractile activity of skeletal muscle of rats (muscle gastrocnemius) 15 d after the initiation of open trauma of different severity was studied for the first time. The structural organization of C60 fullerene nanoparticles in aqueous solution was analyzed by dynamic light scattering and atomic force microscopy techniques. Such biomechanical parameters of muscle gastrocnemius contraction as integrated muscle power, levels of generation of its maximum and minimum force, and time interval until reaching 50% of the level of force response of the muscle were analyzed. Such biochemical indices as concentrations of c-reactive protein, creatinine, and lactate in the rat blood, as well as indices of pro- and antioxidant balance (activities of superoxide dismutase and catalase, the concentration of reduced glutathione) in the blood and muscle tissue of experimental animals, were investigated. It was found that application of water-soluble C60 fullerenes statistically significantly improves biomechanical parameters of contraction of injured muscle gastrocnemius at the level of 30–45 ± 3%, which is confirmed by normalization of biochemical indices in the blood and muscle tissue of rats at the level of 35–50 ± 3% and 20–37 ± 3%, correspondingly, relative to the open injury group. These findings open the possibility of using C60 fullerenes as potential therapeutic nanoagents capable of correcting pathological states of the muscular system during the physiological repair of open injuries.

Проведено порівняння ефектів С60-фуллерену та відомого екзогенного антиоксиданту N-ацетилцистеїну (NAC) на біомеханіку скорочення швидкого (m. soleus) і повільного (m. gastrocnemius) м’язів щурів за розвитку втоми. С60-фуллерен і NAC вводили внутрішньочеревно в одноразових дозах у 1 і 150 мг/кг відповідно за 2 години до початку ініціації м’язової втоми. Показано, що терапевтичний ефект С60-фуллерену щодо корекції часу утримання максимального рівня силової відповіді м’яза після ініціації втоми склав 20% і 25% відповідно для повільних і швидких м’язів, що у 2,5 і 1,7 разів перевищує подібний ефект NAC. Терапевтичне застосування NAC і С60-фуллерену зменшило кількість лактату та креатиніну у крові тварин на 16% і 28% та 12% і 31% відповідно. Одержані результати свідчать про реальну перспективу застосування С60-фуллеренів як потенційних наноаґентів для підвищення ефективности функціонування скелетних м’язів шляхом модифікування механізмів, що відіграють важливу роль у процесі розвитку м’язової втоми.

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.

Creatine is a nitrogen-containing carboxylic acid and a main component of phosphocreatine. In recent years, creatine is considered as a component of dietary nutrition, to improve the efficiency of physical activity and increase muscle mass of athletes and older people. Creatine has been shown to be able restore cardiac contractility impairment after myocardial infarction. However, as muscle cells do not synthesise creatine, the efficiency of creatine depends on its transmembrane transport. In our study, we evaluated the effect of «ProCreatine» (ProCr), a novel membrane transporter-independent creatine modification on fatigability of the rat gastrocnemius muscle and portal vein smooth muscle using fa tigue stimulation pools. Mechanokinetic and biomechanical markers of fatigue in muscles to maintain the level of isometric tension induced by field electrical stimulation were examined. The results indicate that administration of ProCr to skeletal muscle significantly increases maximal force output, integrated muscle contractile force and significantly increases muscle productivity. We observed positive changes in all studied biochemical indices of fatigue. In addition, ProCr increases the duration of sustaining a constant level of isometric contraction in portal vein smooth muscle caused by electrical stimulation by 6 fold. Regular creatine in the same dose had no sig nificant effect on these parameters neither in skeletal nor in smooth muscles. The data obtained suggest the possibility of using ProCr as a therapeutic agent capable of reducing and correcting pathological conditions of the muscular system that arise during the processes of fatigue in skeletal muscles and smooth muscles of hollow organs.

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.

Background. It has been shown that the available therapeutic agents do not eliminate the consequences of miotic pathologies in chronic alcoholism, the most significant of which are disturbances in the dynamics of muscle contraction. A positive effect of biocompatible water-soluble C60 fullerenes on the contraction parameters of damaged muscles has been established. In addition, administration of C60 fullerene aqueous solution during chronic alcoholization of rats protects muscle tissue from damage caused by oxidative stress. Materials and Methods. Biomechanical parameters such as the values of the minimum and maximum contraction force and the muscle force impulse were evaluated using tensometry. The blood levels of creatine phosphokinase and lactate dehydrogenase, creatinine and lactate as well as the level of oxidative processes in muscle tissue of experimental animals (content of hydrogen peroxide, activity of catalase, glutathione peroxidase and superoxide dismutase) as markers of muscle damage were determined using methods of biochemical analysis. Results. The C60 fullerene aqueous solution effect on the skeletal muscle contraction dynamics in rats after chronic alcoholization for 9 months and cessation of alcohol consumption for 1 month was investigated. It was established that water-soluble C60 fullerenes (daily dose of 1 mg/kg) reduce the effects of chronic alcoholization by 35–40±2 % on the studied biomechanical parameters and by 20±1 % on the studied biochemical parameters compared to the group of alcoholized animals, thus increasing the energy capabilities of the muscular system. Conclusions. The obtained data indicate a pronounced protective effect of C60 fullerenes on the muscle soleus contraction dynamics during the development of alcoholic myopathy, which opens up the potential possibility of their use for the prevention and correction of miotic damage.

Muscle fatigue as a defense body mechanism against overload is a result of the products of incomplete oxygen oxidation such as reactive oxygen species. Hence, C60 fullerene as a powerful nanoantioxidant can be used to speed up the muscle recovery process after fatigue. Here, the residual effect of C60 fullerene on the biomechanical and biochemical markers of the development of muscle soleus fatigue in rats for 2 days after 5 days of its application was studied. The known antioxidant N-acetylcysteine (NAC) was used as a comparison drug. The atomic force microscopy to determine the size distribution of C60 fullerenes in an aqueous solution, the tensiometry of skeletal muscles, and the biochemical analysis of their tissues and rat blood were used in this study. It was found that after the cessation of NAC injections, the value of the integrated muscle power is already slightly different from the control (5%–7%) on the first day, and on the second day, it does not significantly differ from the control. At the same time, after the cessation of C60 fullerene injections, its residual effect was 45%–50% on the first day, and 17%–23% of the control on the second one. A significant difference (more than 25%) between the pro- and antioxidant balance in the studied muscles and blood of rats after the application of C60 fullerene and NAС plays a key role in the long-term residual effect of C60 fullerene. This indicates prolonged kinetics of C60 fullerenes elimination from the body, which contributes to their long-term (at least 2 days) compensatory activation of the endogenous antioxidant system in response to muscle stimulation, which should be considered when developing new therapeutic agents based on these nanoparticles.