C60 fullerenes increase the intensity of rotational movements in non­anesthetized hemiparkinsonic rats.

The effect of C60 fullerene aqueous colloid solution (C60FAS) on the intensity of long­lasting (persisting for one hour) rotational movements in non­anesthetized rats was investigated. For this purpose, an experimental hemiparkinsonic animal model was used in the study. Rotational movements in hemiparkinsonic animals were initiated by the intraperitoneal administration of the dopamine receptor agonist apomorphine. It was shown that a preliminary injection of C60FAS (a substance with powerful antioxidant properties) in hemiparkinsonic rats induced distinct changes in animal motor behavior. It was revealed that fullerene­pretreated animals, in comparison with non­pretreated or vehicle­pretreated rats, rotated for 1 h at an approximately identical speed until the end of the experiment, whereas the rotation speed of control rats gradually decreased to 20-30% of the initial value. One can assume that the observed changes in the movement dynamics of the hemiparkinsonic rats after C60FAS pretreatment presumably can be induced by the influence of C60FAS on the dopaminergic system, although the isolated potentiation of the action of apomorphine C60FAS cannot be excluded. Nevertheless, earlier data on the action of C60FAS on muscle dynamics has suggested that C60FAS can activate a protective action of the antioxidant system in response to long­lasting muscular activity and that the antioxidant system in turn may directly decrease fatigue­relate d changes during long­lasting muscular activity.

C60 Fullerene Prevents Restraint Stress-Induced Oxidative Disorders in Rat Tissues: Possible Involvement of the Nrf2/ARE-Antioxidant Pathway.

The effects of C60FAS (50 and 500 µg/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N-acetylcysteine. Oxidative stress biomarkers (ROS, O2·-, H2O2, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, γ-GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH-related enzymes γ-GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis. Under a stress condition, C60FAS attenuates ROS generation and O2·- and H2O2 releases and thus decreases lipid peroxidation as well as increases rat tissue antioxidant capacity. We have shown that C60FAS supplementation has dose-dependent and tissue-specific effects. C60FAS strengthened the antiradical defense through the upregulation of MnSOD in brain cells and maintained MnSOD protein content at the control level in the myocardium. Moreover, C60FAS enhanced the GSH level and the activity/protein expression of GSH-related enzymes. Correlation of these changes with Nrf2 protein content suggests that under stress exposure, along with other mechanisms, the Nrf2/ARE-antioxidant pathway may be involved in regulation of glutathione homeostasis. In our study, in an in vivo model, when C60FAS (50 and 500 µg/kg) was applied alone, no significant changes in Nrf2 protein expression as well as in activity/protein levels of MnSOD and GSH-related enzymes in both tissues types were observed. All these facts allow us to assume that in the in vivo model, C60FAS affects on the brain and heart endogenous antioxidative statuses only during the oxidative stress condition.

Fos immunoreactivity in the intermediolateral nucleus induced by tendon vibration of the m. triceps surae in rats pretreated with a nitric oxide blocker or precursor.

We investigated neuronal activation of the rat intermediolateral (IML) nucleus of the thoracolumbar spinal cord, initiated by Achilles tendon vibration, after intramuscular (m. triceps surae) administration of 7­nitroindazole (7­NI) or L­arginine (LA). The spindle afferent response to vibratory stimuli induced a distinct bilateral increase in the activation of c­Fos immunoreactivity in the spinal neurons in three groups of rats (tendon­vibrated, tendon­vibrated + 7­NI and tendon­vibrated + LA). The T5/T13 segments in tendon­vibrated +7­NI animals showed the highest increase of Fos­immunoreactive neurons. This increase was two times higher than that in tendon only­vibrated control rats and endon­vibrated + LA animals. The highest mean number of labelled neurons were observed in the IML nucleus and in layers 4 and 7 of the T5-L3 segments in tendon­vibrated and tendon­vibrated + 7­NI animals, and in the IML nucleus and layer 4 in tendon­vibrated + LA rats. The highest mean number of activated neurons was found ipsilaterally in the IML nucleus of the T5/T13 segment. These results indicate that decreased nitric oxide release after injection of 7­NI was accompanied by a potentiation of the early c­fos gene expression induced by muscle proprioceptive activity within the thoracolumbar region of the rat spinal cord. Thus, enhanced c­Fos immunoreactivity in the IML nucleus indicated that the sympathetic nervous system can exert a direct influence on the muscle spindles.

C60 Fullerenes Diminish Muscle Fatigue in Rats Comparable to N-acetylcysteine or ß-Alanine.

The aim of this study is to detect the effects of C60 fullerenes, which possess pronounced antioxidant properties, in comparison with the actions of the known exogenous antioxidants N-acetylcysteine (NAC) and ß-Alanine in terms of exercise tolerance and contractile property changes of the m. triceps surae (TS) during development of the muscle fatigue in rats. The electrical stimulation of the TS muscle during four 30 min series in control rats led to total reduction of the muscle contraction force. Furthermore, the effects of prior intraperitoneal (i.p.) or oral C60FAS application and preliminary i.p. injection of NAC or ß-Alanine on muscle contraction force under fatigue development conditions is studied. In contrast to control rats, animals with C60FAS, NAC, or ß-Alanine administration could maintain a constant level of muscle effort over five stimulation series. The accumulation of secondary products and changes in antioxidant levels in the muscle tissues were also determined after the fatigue tests. The increased levels of lactic acid, thiobarbituric acid reactive substances and H2O2 after stimulation were statistically significant with respect to intact muscles. In the working muscle, there was a significant (p < 0.05) increase in the activity of endogenous antioxidants: reduced glutathione, catalase, glutathione peroxidase, and superoxide dismutase. Treated animal groups showed a decrease in endogenous antioxidant activity relative to the fatigue-induced animals (P < 0.05). Oral C60FAS administration clearly demonstrated an action on skeletal muscle fatigue development similar to the effects of i.p. injections of the exogenous antioxidants NAC or ß-Alanine. This creates opportunities to oral use of C60FAS as a potential therapeutic agent. Due to the membranotropic activity of C60 fullerenes, non-toxic C60FAS has a more pronounced effect on the prooxidant-antioxidant homeostasis of muscle tissues in rats.

C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue.

BACKGROUND: Bioactive soluble carbon nanostructures, such as the C60 fullerene can bond with up to six electrons, thus serving by a powerful scavenger of reactive oxygen species similarly to many natural antioxidants, widely used to decrease the muscle fatigue effects. The aim of the study is to define action of the pristine C60 fullerene aqueous colloid solution (C60FAS), on the post-fatigue recovering of m. triceps surae in anaesthetized rats. RESULTS: During fatigue development, we observed decrease in the muscle effort level before C60FAS administration. After the application of C60FAS, a slower effort decrease, followed by the prolonged retention of a certain level, was recorded. An analysis of the metabolic process changes accompanying muscle fatigue showed an increase in the oxidative stress markers H 2 O 2 (hydrogen peroxide) and TBARS (thiobarbituric acid reactive substances) in relation to the intact muscles. After C60FAS administration, the TBARS content and H 2 O 2 level were decreased. The endogenous antioxidant system demonstrated a similar effect because the GSH (reduced glutathione) in the muscles and the CAT (catalase) enzyme activity were increased during fatigue. CONCLUSIONS: C60FAS leads to reduction in the recovery time of the muscle contraction force and to increase in the time of active muscle functioning before appearance of steady fatigue effects. Therefore, it is possible that C60FAS affects the prooxidant-antioxidant muscle tissue homeostasis, subsequently increasing muscle endurance.

The Movement- and Load-Dependent Differences in the EMG Patterns of the Human Arm Muscles during Two-Joint Movements (A Preliminary Study).

Slow circular movements of the hand with a fixed wrist joint that were produced in a horizontal plane under visual guidance during conditions of action of the elastic load directed tangentially to the movement trajectory were studied. The positional dependencies of the averaged surface EMGs in the muscles of the elbow and shoulder joints were compared for four possible combinations in the directions of load and movements. The EMG intensities were largely correlated with the waves of the force moment computed for a corresponding joint in the framework of a simple geometrical model of the system: arm - experimental setup. At the same time, in some cases the averaged EMGs exit from the segments of the trajectory restricted by the force moment singular points (FMSPs), in which the moments exhibited altered signs. The EMG activities display clear differences for the eccentric and concentric zones of contraction that are separated by the joint angle singular points (JASPs), which present extreme at the joint angle traces. We assumed that the modeled patterns of FMSPs and JASPs may be applied for an analysis of the synergic interaction between the motor commands arriving at different muscles in arbitrary two-joint movements.

The Averaged EMGs Recorded from the Arm Muscles During Bimanual "Rowing" Movements.

The main purpose was to analyze quantitatively the the average surface EMGs of the muscles that function around the elbow and shoulder joints of both arms in bimanual "rowing" movements, which were produced under identical elastic loads applied to the levers ("oars"). The muscles of PM group ("pulling" muscles: elbow flexors, shoulder extensors) generated noticeable velocity-dependent dynamic EMG components during the pulling and returning phases of movement and supported a steady-state activity during the hold phase. The muscles of RM group ("returning" muscles: elbow extensors, shoulder flexors) co-contracted with PM group during the movement phases and decreased activity during the hold phase. The dynamic components of the EMGs strongly depended on the velocity factor in both muscle groups, whereas the side and load factors and combinations of various factors acted only in PM group. Various subjects demonstrated diverse patterns of activity redistribution among muscles. We assume that central commands to the same muscles in two arms may be essentially different during execution of similar movement programs. Extent of the diversity in the EMG patterns of such muscles may reflect the subject's skilling in motor performance; on the other hand, the diversity can be connected with redistribution of activity between synergic muscles, thus providing a mechanism directed against development of the muscle fatigue.

Dynorphin B induces lateral asymmetric changes in feline spinal cord reflexes.

The effects of dynorphin B (an agonist of κ-opioid receptors) and naloxone (an antagonist of opioid receptors) on the field potentials (FPs) evoked in the lumbar spinal cord of spinalized cats were examined following successive stimulation of pairs of identical peripheral nerves on both sides of the body. The FPs were recorded bilaterally using microelectrodes from symmetrical sites of the gray matter between the L6 and L7 segments of the spinal cord transected at level of Th11. Significant changes (up to 75%) were registered in the areas of the initial positive components of the FPs evoked by sequential stimulation of the nn. gastrocnemius-soleus, flexor digitorum longus, and tibialis at both hind limbs; a difference between the effects of various nerves was not observed. Two-Way ANOVA analysis showed that two factors, the injection type and recording side, as well as a combination of these factors, strongly influenced the amplitudes of the FPs. Statistically significant side- and injection-dependent differences were registered in the majority of the tests. Both the directions of the changes in the FPs and their relative amplitudes were not strongly connected with a definite side of the spinal cord in different animals. Therefore, it is possible to postulate that the κ-opioid receptors are distributed inhomogeneously over the neuronal populations transmitting the peripheral afferent signals from different hind limbs, thus indicating a possible presence of the lateral asymmetry effects.