Structure and biological activity of particles produced from highly activated carbon adsorbent.

Over the recent years, carbon particles have gained relevance in the field of biomedical application to diminish the level of endo-/exogenous intoxication and oxidative stress products, which occur at different pathological states. However, it is very important that such carbon particles, specially developed for parenteral administration or per oral usage, possess a high adsorption potential and can remove hazard toxic substances of the hydrophilic, hydrophobic and amphiphilic nature usually accumulated in the blood due to the disease, and be absolutely safe for normal living cells and tissues of organism. In this work, the stable monodisperse suspension containing very small-sized (Dhydro = 1125.3 ± 243.8 nm) and highly pure carbon particles with an excellent accepting ability were obtained. UV-spectra, fluorescence quenching constant and binding association constant were provided by the information about conformational alterations in an albumin molecule in presence of carbon particles, about the dynamic type of quenching process and low binding affinity between carbon and protein. The later was confirmed by DSC method. In vitro cell culture experiments showed that carbon particles did not possess any cytotoxic effect towards all testing the normal cell lines of different histogenesis, did not show genotoxic effects and were absolutely safe for experimental animals during and after their parenteral administration. These observations may provide more information about how to develop a safe preparation of carbon particles for different biomedical applications, in particular, as a mean for intracorporeal therapy of various heavy diseases accompanied by the increased endogenous intoxication and the level of oxidative stress.

Biological activity of cerium dioxide nanoparticles.

Cerium dioxide nanoparticles (CeO2 NPs) with a high value of ζ-potential (≥30 mV) have been synthesized in reverse microemulsions and they are able to form the high-stable aqueous suspension without any additional stabilizers. It has been shown that the interaction of such CeO2 NPs with transport proteins, such as BSA, affects their molecular conformation and biochemical activity. The observed changes in the UV-absorbance spectrum and intrinsic fluorescence quenching of BSA molecule are indicative of the occurrence of structural changes caused by binding with the surface of CeO2 NPs. Low affinity between BSA and CeO2 NPs has been confirmed by differential scanning calorimetry (DSC). Moreover, CeO2 NPs can act as regenerative free-radical scavengers, and their antioxidant activity depends on the concentration. The positive charge of CeO2 NPs can be attributed to their low toxicity toward human malignant lymphocytes MT-4 and breast cancer cells MCF-7 however, the morphofunctional features of MCF-7 cells interacting with CeO2 NPs are indicative of the decrease in oncogenicity.

The effect of two formulations of carbon enterosorbents on oxidative stress indexes and molecular conformation of serum albumin in experimental animals exposed to CCl4.

The liver failure means inability to perform its normal synthetic, biotransformation and excretory functions. The disturbance of metabolic processes leads to the development of "metabolic endogenous intoxication" resulting in oxidative stress. Oxidative stress initiates the processes of oxidation of amino acid residues of blood plasma proteins causing the changes in their structure and functions. The effect of administration of highly activated porous carbonic enterosorbents on oxidative stress manifestations and molecular conformation of serum albumin in blood of experimental animals with acute liver failure induced by carbon tetrachloride (CCl4) needs to be investigated. Two forms of activated carbonic enterosorbents such as AC1 (primary beads with the range of diameters of 125-250 µm) and AC2 (secondary granules prepared from micronized AC1 having the mean particle size of ~1 µm) derived from phenol-formaldehyde resin were used in rat model with CCl4 intoxication. The total level of reactive oxygen species (ROS) in blood plasma, the activity of catalase (CAT) in blood hemolysates; the content of reduced glutathione (GSH) in liver homogenates, and the level of oxidative modification of proteins (OMP) such as aldehyde-dinitrophenylhydrazone (A-DNPH) and ketone-dinitrophenylhydrazone (K-DNPH) derivatives in blood plasma and liver homogenates were determined. In addition, the level of pro/antioxidant ratio in blood hemolysates and the content of lipid peroxidation product - malondialdehyde (MDA), in blood plasma and liver were determined. Melting thermograms of blood plasma proteins (BPP) and molecular conformation changes of serum albumin were analyzed by biophysical methods (differential scanning microcalorimetry and spectrofluorimetry). The extent of CCl4-induced oxidative damage in blood and liver of experimental animals was shown to be less expressed for AC1 in comparison with AC2 enterosorbent. However, AC2 used in the form of secondary granules positively influenced some biophysical properties of albumin molecule (temperature of melting, shape of melting endotherm and intrinsic fluorescence) after rats exposure to CCl4. In general, administration of both AC1 and AC2 led to the reduction of oxidative stress manifestations and partial restoration of native molecular conformation of serum albumin. These observations are promising in terms of achieving recovery of detoxification potential of organism after severe liver injury.