Experimental assessment of the oncoprotective properties of low-molecular chitosan and its effects on cytostatic and radiation myelosuppression

Background. Currently, targeted therapy is the most promising method of treating malignant neoplasms. It is mainly used as a secondline therapy, along with classical methods of chemotherapy and radiation therapy. Among the areas of targeted cancer therapy, the most intensively developing areas are monoclonal antibodies and low-molecular-weight biologically active substances, tyrosine kinase blockers, folic acid receptors and serine/threonine kinase blockers. There is another area of targeted therapy, which is based on the selective activation of the cellular component of the immune system, primarily macrophages. Macrophages and T-lymphocytes are the main, genetically determined link for the elimination of tumor cells using natural pathophysiological mechanisms. The purpose of this work is to evaluate the oncoprotective effect of low–molecular-weight chitosan on an in vivo model of a transferable malignant tumor and to investigate the effectiveness of the therapeutic effect of chitosan in leukopenia induced by cytostatics and gamma radiation.

Materials and methods. Cytostatic leukopenia: 15 outbred nonlinear laboratory ICR (CD-1) mice (males) With an average body weight of 20-22 g, they were divided into 3 groups of 5 animals in each group. Cytostatic leukopenia was modeled by a single intraperitoneal injection of cyclophosphamide solution to animals of all groups at the rate of 250 mg cyclophosphamide per 1 kg of animal body weight. Radiation leukopenia: 10 outbred nonlinear laboratory ICR (CD-1) mice (males) With an average body weight of 20-22 g, they were divided into 2 groups of 5 animals in each group. Radiative leukopenia of moderate severity was modeled by a single exposure to gamma braking radiation at a dose of 0.9 Gy on an ILU-10 pulsed linear accelerator. Investigation of the antitumor activity of low-molecularweight chitosan on an in vivo transferable tumor model: a cyclophosphamide-resistant solid form of mouse lymphosarcoma RLS 40 was used as a transferable tumor. To form a solid tumor, 22 outbred nonlinear laboratory ICR (CD-1) mice (males) were transplanted with lymphosarcoma from RLS 40 mice.

Results. As a result of the study, it was found that low-molecular-weight chitosan has therapeutic efficacy in cytostatic leukopenia, and its effectiveness was more pronounced with enteral administration. Based on the results of the study, it can be argued that enteral administration of low-molecular-weight chitosan, starting 2 days after administration of cytostatic, may be a very promising way to compensate for cytostatic myelosuppression and may significantly improve the effectiveness of treatment and quality of life of cancer patients. There is a pronounced therapeutic effect from the use of low-molecular-weight chitosan in compensation of moderate-grade radiation leukopenia. Low molecular weight chitosan has a pronounced oncoprotective effect on an experimental model of a solid form of mouse lymphosarcoma.

The volume and weight of a solid tumor in the experimental group 1 is almost two times lower than in the control group.

Conclusion. The data obtained allow us to consider low molecular weight chitosan as a very promising auxiliary agent in the treatment of malignant tumors by traditional methods of chemoradiotherapy. Low molecular weight chitosan is a part of enterosorbents. Due to its unique technology, this component is stable in the environment of the small and large intestines at a pH of up to 8.2, which distinguishes it from analogues that are stable only at acidic pH values. Compensation of cytostatic and radiation leukopenia by taking an aqueous solution of low molecular weight chitosan as part of enterosorbents. It can be an effective and safe way to reduce the complications of chemoradiotherapy and improve the quality of life of cancer patients. Preliminary data on the assessment of the oncoprotective effect of low-molecular-weight chitosan and enterosorbents based on it allow us to consider it as a safe means of preventing cancer, especially at the initial stage, but this requires further research on various models of transferable tumors.

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