Effect of Primary and Secondary Beads of Carbon Enterosorbent on Haematological Parameters and Oxidative Stress Development Caused by Melphalan in Rats.

Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer-Emmett-Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1-primary beads with the particle size range of 125-250 µm, and AC2-micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde-dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

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.