Ultrastructural and General Toxic Parallels of Pegylated Hyaluronidase

The assortment of medicinal preparations with the active substance hyaluronidase is very diverse. The development of a prototype of the drug pegylated hyaluronidase (PEG-GIAL) per os is very relevant. The aim of the work is toxicological evaluation of safety of PEG-GIAL effect on the liver in in vitro and in vivo experiments. We used the transplanted cell culture of human hepatocytes, outbred sexually mature white rats, and chinchilla rabbits. The results of electron-microscopic study showed that the addition of PEG-GIAL in the studied doses led to an increase in the content and size of microvilli on the outer membrane of hepatocytes, an increase in the content of protein synthesis structures of cells, changes in the shape, size, electron density, the content of mitochondrial cristae, changes in the content of autophagic structures. The viability of hepatocytes at addition of PEG-GIAL in the studied doses was at the level of control. Introduction of PEG-GIAL in the studied doses to rats had an effect on blood biochemical parameters, which had a random non-dose-dependent character, while in rabbits it had no effect. Pathomorphological study showed that practically in all rats both in control and in experiment there are small sizes perivascular and focal lympho-macrophage infiltrates in lobules, in female rats small fatty dystrophy of hepatocytes more expressed in cells located around veins. In rabbits moderate venous full blood flow, bar structure of lobules is not disturbed, hepatocytes without signs of dystrophy.