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

Abstract

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.

Keywords

• oxidative stress
• myelotoxicity
• anti-cancer chemotherapy
• rats
• melphalan
• enterosorption