EXPERIMENTAL STUDY OF THE EFFECT OF PEGYLATED HYALURONIDASE ON HEMATOLOGIC PARAMETERS AND HEMATOPOIESIS
Authors:   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Shvetsova A.M. ,   Goldberg Research Institute of Pharmacology and Regenerative Medicine, Korolev M.A. ,   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences;, Churin A.A. ,   Goldberg Research Institute of Pharmacology and Regenerative Medicine, Ershov K.I. ,   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical University, Madonov P.G. ,   Institute of Clinical and Experimental Lymphology, Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical University
Published: December 2024

Introduction. One of the stages in the development of medicinal products (MP) is the study of safety assessment. Determination of possible toxic effects, establishment of the nature and severity of the damaging effect of drugs under development during their administration is carried out, including studying the effect on hematologic parameters and hematopoiesis.
Aim. To assess the possibilities of PEG-HYAL impact on hematologic parameters and hematopoiesis when administered per os.
Material and methods. Hyaluronidase immobilized by electron beam synthesis on polyethylene oxide (PEG-HYAL). Laboratory animals – white mature conventional outbred rats and chinchilla rabbits. Hematological parameters were determined using an automatic hematological analyzer Abacus (Diatron, Austria) and conventional manual methods of research. The effect of PEG-HYAL on the state of medullary hematopoiesis was determined by counting the total number of myelokaryocytes per femur (106/femur) and myelograms on smears (in rats). The percentage of individual cell forms in rat myelogram counts was converted to absolute numbers, x106 cells per femur. In rabbits, the myelogram indices of bone marrow, taken from the sternum segment, were determined in relative units (%) only.
Results. The analysis of the obtained results of the effect of PEG-HYAL administration on hematologic indices in rats (male and female) did not show any pathological changes. The revealed changes in hematologic parameters in rats are neither significant, nor systemic and dose-dependent. PEG-HYAL administration to rabbits has no toxic effect on hematologic parameters with multiple intragastric administration. Administration of PEG-HYAL for 28 days to rats in all studied doses does not produce a toxic effect on the main studied bone marrow parameters. While the revealed changes in the quantitative composition of myelokaryocytes are non-systemic and reversible. PEG-HYAL administration has no toxic effect on bone marrow indices of rabbits when administered intragastrically in the studied doses during 28 days.
Conclusion. Interpretation of the obtained results, concerning the effect of the per os PEG-HYAL administration to experimental animals on hematologic parameters and hematopoiesis, can be used as a preclinical dossier of the drug.