Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro
A. M. Shvetsova,
M. A. Korolev,
A. A. Churin,
N. A. Bondarenko,
N. P. Bgatova,
K. I. Ershov,
P. G. Madonov,
Yu. R. Ravilova,
S. V. Mishenina https://doi.org/10.31549/2542-1174-2024-8-3-51-61
Abstract
I n t r o d u c t i o n. 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.
A i m. Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro.
M a t e r i a l s a n d m e t h o d s. 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.
R e s u l t s. 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.
C o n c l u s i o n. 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.
About the Authors
A. M. Shvetsova
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Alexandra M. Shvetsova – Junior Researcher, Laboratory of Experimental and Clinical Pharmacology, Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.
2, Timakova str., Novosibirsk, 630060
M. A. Korolev
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Maxim A. Korolev – Dr. Sci. (Med.), Head, Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.
Novosibirsk
A. A. Churin
Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
Alexey A. Churin – Dr. Sci. (Med.), Chief Researcher, Head, Department of Drug Toxicology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of the Russian Academy of Sciences.
Tomsk
N. A. Bondarenko
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Natalia A. Bondarenko – Cand. Sci. (Bio.), Head, Laboratory of Experimental and Clinical Pharmacology, Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.
Novosibirsk
N. P. Bgatova
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Natalia P. Bgatova – Dr. Sci. (Bio.), Professor, Head, Laboratory of Ultrastructural Studies, Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.
Novosibirsk
K. I. Ershov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical University
Russian Federation
Russian Federation
Konstantin I. Ershov – Cand. Sci. (Bio.), Associate Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University; Senior Researcher, Laboratory of Pharmaceutical Technology, Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.
Novosibirsk
P. G. Madonov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical University
Russian Federation
Russian Federation
Pavel G. Madonov – Dr. Sci. (Med.), Associate Professor, Head, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University; Head, Department of Experimental Pharmacology, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics.
Novosibirsk
Yu. R. Ravilova
Novosibirsk State Medical University
Russian Federation
Russian Federation
Yulia R. Ravilova – Cand. Sci. (Med.), Associate Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University.
Novosibirsk
S. V. Mishenina
Novosibirsk State Medical University
Russian Federation
Russian Federation
Svetlana V. Mishenina – Dr. Sci. (Med.), Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University.
Novosibirsk
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Review
For citations:
Shvetsova A.M., Korolev M.A., Churin A.A., Bondarenko N.A., Bgatova N.P., Ershov K.I., Madonov P.G., Ravilova Yu.R., Mishenina S.V. Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro. Journal of Siberian Medical Sciences. 2024;(3):51-61. (In Russ.) https://doi.org/10.31549/2542-1174-2024-8-3-51-61
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