Laboratory of Pathological Physiology and Experimental Therapy, Institute of Pharmacology of RAMS SD Tomsk, Russia
Abstract:
In this study was found antifibrotic activity of pegylated hyaluronidase (pegHYAL) (“Scientific Future Management”, Novosibirsk, Russia) on the models partially reversible and irreversible bleomycin-induced pneumofibrosis in C57BL/6 mice. PegHYAL has high antifibrotic activity under prophylactic and therapeutic modes of administration. Intranasal inoculation of pegHYAL blocks bleomycin-induced lung injury and fibrosis. Intravenous injection and enteral introduction of pegHYAL does not block. These results demonstrate the intraperitoneal spiperone injection reduces infiltration of alveolar interstitium and alveolar passages by inflammatory cells and prevents the growth of connective tissue in the lung parenchyma. Antifibrotic effect of the sequential assignment pegHYAL (therapeutic intranasal administration) and spiperone surpasses the activity of isolated compounds: collagen deposition in the lung parenchyma is not registered. It was found that accelerated recovery histo-structure of lung influenced by consistently compounds is a result of sum of the effects pegHYAL (decrease alveolar interstitial infiltration hematopoietic stem cell (HSCs) and fibroblast colony-forming units (CD45-), restoration of endothelial cells in the lungs (CD45neg, CD31neg, CD34neg)) and spiperone (suppression of bone marrow HSCs and progenitor hematopoietic cells in the lungs, increase the number of endothelial cells and decreased proliferation and differentiation of mesenchymal multipotent stem cells) in bleomycin-induced damage of lung. These data suggest that the violation of the structural and spatial organization of the hyaluronan matrix followed by modulation of endogenous stem cells is a new and promising approach for the treatment of pulmonary fibrosis.