Interleukins and metalloproteinases in the lungs of mice with BCG-granulomatosis with the injection of the liposomal form of dextrazide

DOI: https://doi.org/10.29296/24999490-2024-04-07

A.M. Sinyavskaya, A.V. Troitskii, T.N. Bystrova, E.G. Novikova, V.G. Selyatitskaya
Federal State Budget Scientific Institution “Federal Research Center of Fundamental and Translational Medicine”,
Timakova str., 2, Novosibirsk, 630117, Russian Federation

Introduction. An actual decision of the issue of safety and effective drug therapy improvement is the development of transport systems that allow to provide targeted delivery of drugs to target cells, while reducing their toxic effects. The aim of the work was to carry out a comparative study of the effects of isoniazid, composition of isoniazid with oxidized dextran (dextrazid), and liposomal form of dextrazid (LFD) on the levels of interleukins IL-6 and tumor necrosis factor-α (TNF-α), metalloproteinases MMP1 and MMP9, tissue inhibitor of proteinase TIMP1, volume density of destruction and lymphoid infiltrates in the lung parenchyma of mice with BCG-granulomatosis. Material and Methods. The study was performed on 100 male BALB/c mice, the tested substances were injected for 2 and 6 months. Lungs were fixed in 10% buffered formalin solution and subjected to standard histologic staging. To estimate the volume density of destructive changes and lymphoid infiltrates, the percent of area occupied by them was determined; in immunohistochemical study, the volume density of positively stained cells was determined. Results. It was shown that the effectiveness of dextrazide in comparison with isoniazid regarding the reduction of inflammatory processes activity in the lungs is higher, with the greatest effectiveness of LFD injected by inhalation. In response to isoniazid injection into mice, the levels of MMP1 and MMP9 decreased more than twice, and the level of TIMP1 increased; LFD injection intraperitoneally and inhaled caused a more pronounced effect. The level of destructive changes in the lung parenchyma of mice was maximal in mice in the comparison group and minimal in animals injected with LFD regardless of the form of its injection. Conclusion. The results of the study indicate that oxidized dextran in composition with isoniazid contributes to an additional reduction in the activity of inflammatory processes in the lungs of mice with BCG granulomatosis; placing the composition in liposomes enhances the anti-inflammatory effect and contributes to the reduction of destructive processes by decreasing MMP activity and increasing TIMP1 activity.
Keywords: 
isoniazid, compositions of isoniazid with oxidized dextran, BCG granulomatosis, inflammation, interleukins, matrix metalloproteinases
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