Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro
Authors:   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Shvetsova A.M. , Korolev M.A. ,   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Churin A.A. ,   Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia, Bondarenko N.A. ,   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Bgatova N.P. ,   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Ershov K.I. ,   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Novosibirsk State Medical University, Novosibirsk, Russia, Madonov P.G. ,   Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Novosibirsk State Medical University, Novosibirsk, Russia, Ravilova Yu.R. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Mishenina S.V. ,   Novosibirsk State Medical University, Novosibirsk, Russia
Published: September 2024

Introduction. Testicular hyaluronidase preparations are widely used in medical practice. Modification of native biologically active molecules by electron beam PEGylation allows to improve their pharmacokinetic properties, which determines a subsequent improvement of pharmacodynamic effects. The development of an original oral drug with a pharmacologically active core, which is hyaluronidase, is promising, but requires studying the safety of use at the preclinical stage. Aim. Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro. Materials and methods. The object of a study was testicular hyaluronidase PEGylated on polyethylene oxide (PEG-HYAL) using electron beam synthesis. The culture medium is a continous culture of human liver cells Chanq liver. The cytotoxic effect was detected by the MTT assay. Ultrastructural changes were evaluated by electron microscopy. Results. The original drug PEG-HYAL in the studied concentrations of 37, 75 and 150 U/ml has no cytotoxic effect on the human liver cell culture (hepatocytes). Cell viability is virtually at the control level when PEG-HYAL administration at concentrations of 37 and 75 U/ml, and in the maximum concentration of 150 U/ml, cell proliferation is stimulated significantly, as evidenced by an increase in cell viability up to 106%. The results of evaluation of ultrastructural changes in hepatocytes showed that exposure to PEG-HYAL in all concentrations leads to the enhancement of metabolic processes in cells, development of autophagy, which is one of the main homeostatic processes. Conclusion. The drug PEG-HYAL in all studied concentrations has no toxic effect on the human hepatocyte culture. The results obtained can be used in further research in the development of PEG-HYAL.