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Skurikhin E.G.,Research Institute of Pharmacology | Pershina O.V.,Research Institute of Pharmacology | Reztsova A.M.,Research Institute of Pharmacology | Ermakova N.N.,Research Institute of Pharmacology | And 7 more authors.
PLoS ONE | Year: 2015

Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA). To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL) by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL). Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem/progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF)-β, interleukin (IL)-1β, tumor necrosis factor (TNF)-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen) in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31-CD34-CD45-CD44+CD73+CD90+CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan matrix can be considered as a new strategy in treatment of pneumofibrosis. © 2015 Skurikhin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Dygai A.M.,Russian Academy of Medical Sciences | Zyuzkov G.N.,Russian Academy of Medical Sciences | Zhdanov V.V.,Russian Academy of Medical Sciences | Udut V.V.,Russian Academy of Medical Sciences | And 3 more authors.
Recent Patents on Regenerative Medicine | Year: 2013

Nanotechnological modifiers of progenitor cells functions - immobilized (im) granulocyte colony stimulating factor (G-CSF) and hyaluronidase (HD) have been created with the help of ionization radiation. The drugs' effect on the function of progenitor cells of different classes and regenerative activity of these substances have been described. Hepatoprotective, cerebroprotective and hemostimulating effects of imG-CSF and hepatoprotective and hemostimulating properties of imHD have been demonstrated in the experiment. It has been established that the regenerative effect of imG-CSF on the blood system is connected with its influence on the hematopoietic precursors of hematopoietic tissue, and therapeutic effects under chronic hepatitis and hypoxic encephalopathy are determined by the mobilization and migration of multipotent progenitor cells of bone marrow in the target-organ. The stimulation of regional stem cells (SC) of affected tissues can be considered mechanisms of regenerative action of imHD. In addition, the mobilization and homing of bone marrow SC in the liver have the significant importance in realizing imHD therapeutic effects for chronic hepatitis. The drugs' effects are determined by modification of the state of the tissue extracellular matrix, changes in the functioning of microenvironment cells and properties of the progenitor cells themselves. The relevant patents are discussed. © 2013 Bentham Science Publishers.

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