C60 Fullerene Aqueous Solution Research Articles

The effect of C60 fullerenes on the recovery of muscle soleus contraction dynamics in rats after chronic alcoholization

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.

C60 fullerene nanoparticles permeability through the model lipid envelope of coronavirus and their anticoronavirus effect in the in ovo system

Background: An urgent problem of modern biomedicine is the search for potential ways to reduce the spread of coronavirus infections in human and animal populations and eliminate the impact of coronavirus on their bodies. Aim of the work was to determine the structural organization of C60 fullerenes in a model cell medium, to assess their potential ability to penetrate the model lipid envelope of a coronavirus, thus destroying its integrity, as well as the effectiveness of the anticoronavirus action in the in ovo system. Methods: The research was conducted using the Gromacs 2020 software package and the Charmm36 force field. The CHARMM-GUI web resource was used to construct the lipid envelope of a coronavirus. Virological and toxicological methods were used in the in ovo experiments. Results: It is shown that at the initial stages of molecular dynamics C60 fullerene forms small nanoclusters in the amount of 7–16 molecules, which is affected by the initial concentration of C60 fullerene in a model cell medium. At the same time, the shape of nanostructures for the number of molecules over 16 may differ from the correct spherical shape. It was established that C60 fullerene and its nanoclusters are able to penetrate inside the lipid envelope of a coronavirus. In particular, a single C60 molecule can migrate, completely embed itself in the lipid envelope, or move within it. It was found that C60 fullerene aqueous solution, at the maximum permissible concentration (MPC) of 30 μg/embryo, reduces the infectious activity of the chicken infectious bronchitis (CIB) coronavirus when it is used 1, 2 and 4 h after the infection of a sensitive biological system with a coronavirus. Conclusions: It is shown that aggregation of C60 fullerene in a model cell medium can occur in different ways: either before penetration into the lipid envelope of a coronavirus, or inside it. C60 fullerenes, both individually and as part of nanoclusters, are able to form pores in the envelope of a coronavirus, destroying its integrity, which possibly leads to disruption of the corresponding stages of its replication cycle and attachment to cell receptors. It was established that C60 fullerene aqueous solution, when used in the MPC value, shows antiviral activity against the CIB coronavirus in its early stages of interaction with the cell (1–4 h).

C(60) fullerene attenuates the signs of acute renal failure in rats under rhabdomyolysis due to inhibition of oxidative stress

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

Water-soluble pristine C60 fullerenes attenuate isometric muscle force reduction in a rat acute inflammatory pain model

BackgroundBeing a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain.MethodsTo induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension.ResultsIn response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats.ConclusionsThe attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.

The effect of water-soluble pristine C60 fullerene on 6-OHDA-induced Parkinson’s disease in rats

Oxidative stress is thought to be one of the mechanisms that leads to the dysfunction and degeneration of dopaminergic neurons in Parkinson’s disease pathogenesis and presumed to be underway during the prodromal phase. Therefore, therapy, which is effective against pre-motor symptoms, might be effective in preventing or delaying the development and progression of Parkinson’s disease. The aim of our study was to investigate the therapeutic efficiency of pristine C60 fullerene aqueous solution (C60FAS) during Parkinson’s disease in rats. The unilateral dopamine deficiency was induced in male Wistar rats (220–250 g) by stereotaxic microinjection of neurotoxin 6-hydroxydopamine (6-OHDA, 12 μg). C60FAS was injected to rats intraperitoneally daily for 10 days (0.65 mg/kg per day). The percentage of destroyed dopaminergic neurons was determined by the apomorphine test and by IHC staining of tyrosine hydroxylase-positive neurons in substantia nigra. We evaluated the rat body weight, the water and food intake, Open Field behavioural test, the level of biochemical antioxidant system, the activity of peritoneal macrophages. Levels of spontaneous and carbachol-stimulated colon motility were estimated by ballonographic method in vivo. C60FAS showed a positive tendency to increase the number of tyrosine hydroxylase-positive cells in the midbrain, which was associated with more profound improvement in apomorphine-rotation behaviour and slight relief of the anxiety level in Open Field test. Furthermore, C60FAS treatment increased the index of stimulated distal colon motor activity while it did not have a significant effect on water content in feces and total gastrointestinal transit time. C60FAS treatment did not affect water intake behaviour or body weight changes while it induced an increase of glutathione level and decrease activity of glutathione peroxidase in the brain as well as an increase in activity of peritoneal macrophages in 6-OHDA-Parkinson’s disease rats. These findings confirmed the potential therapeutic effectiveness of water-soluble pristine C60 fullerene in Parkinson’s disease pathogenesis, though there is ground for caution because of its systemic mild toxic effect.

Does C60 fullerene act as a transporter of small aromatic molecules?

C60 fullerene is reported to directly interact with biomolecules, such as aromatic mutagens or anticancer drugs. Therefore, it is extensively studied for its potential application in the fields of drug delivery and chemoprevention. Understanding the nature of fullerene-drugs interactions might contribute to optimization and modification of the existing chemotherapy systems. Possible interactions between ICR-191, a model acridine mutagen, with well-established biophysical properties and mutagenic activity, and C60 fullerene aqueous solution were investigated by broad range of biophysical methods, such as Dynamic Light Scattering, Isothermal Titration Calorimetry, and Atomic Force Microscopy. Additionally, to determine biological activity of ICR-191-C60 fullerene mixtures, Ames mutagenicity test was employed. It was demonstrated that C60 fullerene interacts non-covalently with ICR-191 and has strong affinity to bacterial membranes. The obtained results provide practical insight into C60 fullerene interactions with aromatic compounds.

Effect of C60 fullerene nanoparticles on the diet-induced obesity in rats

Obesity is a growing global health problem. Since increased oxidative stress is one of the key pathological mechanisms underpinning overweight and strongly correlates with progression of obesity-related complications we hypothesized that C60 fullerene nanoparticles, due to their strong antioxidant capacity, could be the promising therapeutic agent in the treatment of this disease. Here we investigated whether the C60 fullerenes can alleviate diet-induced obesity (DIO) and metabolic impairments associated with it. To determine the effect of C60 fullerenes on some nutritional and metabolic parameters, rats were fed either a normal diet (6.7% fat, 15.27 kJ·g-1) or a high-fat diet (38.8% fat, 28.71 kJ·g-1) for 70 days and were simultaneously treated per os with pristine C60 fullerene aqueous solution (C60FAS; 0.3 mg·kg-1 every other day) since the 28th day from the start of the experiment. Rats fed with high fat diet had significantly increased body mass index (BMI), levels of insulin, glucose, glycosilated hemoglobin (HbA1c) and serum pro-inflammatory cytokines compared with control rats fed with low-fat chow. C60 fullerenes normalized the metabolic parameters and partially reduced BMI in DIO animals. Pro-inflammatory cytokines (IL-1b, IL-12, INFγ) were also decreased in serum of DIO rats treated with C60 fullerenes while anti-inflammatory cytokines (IL-4, IL-10) were at the control levels. High fat diet caused the increased level of oxidative stress products, and this was accompanied by decreased activity both the superoxide dismutase and catalase, whereas the administration of C60 fullerenes markedly decreased level of oxidative stress and enhanced antioxidant enzyme activities. These data indicate that water-soluble pristine C60 fullerenes reduce chronic inflammation, restore glucose homeostasis as well as positively affects on prooxidant-antioxidant homeostasis. C60 fullerenes could be represented as a promising therapeutic agent in the treatment of obesity and its related complications.

Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo

The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

On the Origin of C60 Fullerene Solubility in Aqueous Solution

In this work, we report that the surface hydroxylation of C60 molecules is the most likely mechanism for pristine C60 fullerenes/C60 fullerene aggregate stabilization in water, being independent of the method of C60 fullerene aqueous solution preparation.

C60 FULLERENE EFFECT ON THE DYNAMICS OF FATIGUE PROCESSES IN RAT SOLEUS MUSCLE AFTER ISCHEMIA-REPERFUSION

43 The purposeful application of bio compatible nanomaterials of low toxicity is a relevant problem in modern biotechnology. It is assumed that the use of nanoparticles will help to solve the problems of early disease diagnostics and targeted delivery of drugs into tissues and cells, as well as new methods of selective therapies. C60 fullerene has a prominent position among other potentially effective therapeutic agents [1]. It is known that C60 molecule normalizes cellular metabolism and neural processes, increases resistance to stress, exhibits antiviral properties, has pronounced anti-inflammatory and anti-allergic effects, enhances activity of enzymes and regenerative capacity of tissues [1]. Finally, C60 fullerene and its derivatives can be used for the treatment of cancer [2–4]. C60 fullerene can be readily dissolved in organic solvents, yet it is practically insoluble in water [5]. Poor solubility in water severely hampers investigation of physiological and pharmacological effects of C60 fullerene. As a consequence, a number of C60 fullerene derivatives with better solubility in polar solvents have been synthesized to date [5–6]. Pristine C60 fullerene aqueous solution (С60FAS) has been received by transferring C60 molecules from toluene to water followed by sonication [7–8]. The dark brown solution was identified to be a typical colloid system containing a single C60 molecule and spherical clusters with the diameter of 2–3 nm or more (depending on the C60 fullerene concentration in water) in a hydrated state [7–9]. Due to its nanoscale dimensions, the watersoluble pristine C60 fullerene can penetrate the cell membrane [10]. Toxicity is a major concern for the use of C60 fullerene-containing drugs for biomedical УДК 546.26.043

Equation of State for C60 Fullerene Aqueous Solutions

In the present work PVT data of the C60 fullerene aqueous solution (C60 FAS) were measured as a function of the concentration of C60 molecules using the variable cell method with metal bellows in the temperature range from 295 to 360 K at pressures from 0.1 to 103.2 MPa. On the liquid–vapor equilibrium line the density (ρ) of the C60 FAS was measured using the pycnometer method. As a result, numerical values for the isothermal modulus of elasticity (K T ), isobaric expansivity (α P ), isothermal deviation of entropy factor (TΔS), enthalpy (ΔH), and internal energy (ΔU) have been determined. Finally, an equation of state for the C60FAS was obtained for the first time.