Effects of Dextrazide on Metabolism of Extracellular Matrix in Mouse Organs during Chronic BCG-Induced Granulomatosis
https://doi.org/10.58838/2075-1230-2025-103-3-79-87
Abstract
The objective: to study effects of dextrazide on fibrotic complications in the organs of mice with chronic BCG-induced inflammation.
Subjects and Methods. We used intact mice and animals that were given the BCG vaccine. Six months after the infection, infected mice were administered NaCl and dextrazide intraperitoneally for three months, after which inter-organ remodeling of the extracellular matrix was assessed.
Results. Dextrazide exhibited antifibrotic activity, the mechanisms of which varied between organs. In the liver, fibrosis reduction was achieved mainly through collagen degradation, in the lungs through collagen degradation and suppression of collagen synthesis, and in the spleen through suppression of synthesis. Additionally, the levels of hyaluronan and perlecan decreased in all organs, especially in the lungs, while the levels of galactose in proteoglycans increased. Changes in collagen and proteoglycan metabolism were associated with the local regulation system of the extracellular matrix. Administration of dextrazide caused an elevated activity of degrading enzymes (hyaluronidases and matrix metalloproteinases) in the liver and, especially, in the spleen, while their activity in the lungs remained at the level in the infected mice. At the same time, the level and activity of protease inhibitors (tissue inhibitors of metalloproteinases-1 and -2, α2-macroglobulin) were reduced in the liver and lungs, while in the spleen, on the contrary, their levels were elevated and corresponded to the level in the infected mice.
Keywords
tuberculosis,
collagen,
hydroxyproline,
dextrazide,
matrix metalloproteinases/tissue inhibitors of metalloproteinases,
hyaluronidases,
α2-macroglobulin
Supporting agencies: The authors would like to express their gratitude to A.V. Troitskiy, Ph.D., and his colleagues for providing samples of dextrazide. The work was performed as part of State Assignment No. 122032300155-4 using equipment from TSKP Sovremennyye Opticheskiye Sistemy i TSKP Spektrometricheskiye Izmereniya FITS FTM.
About the Authors
L. B. Kim
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Lena B. Kim, Doctor of Medical Sciences, Chief Researcher, Head of Connective Tissue Biochemistry Group, General Pathology Department
2 Timakova St., Novosibirsk, 630060
Phone: + 7(383)274-94-97
A. N. Putyatina
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Anna N. Putyatina, Candidate of Medical Sciences, Researcher of Connective Tissue Biochemistry Group, General Pathology Department
2 Timakova St., Novosibirsk, 630060
Phone: + 7(383)274-94-97
G. S. Russkikh
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Galina S. Russkikh, Candidate of Biological Sciences,
Senior Researcher of Medical Biotechnological Laboratory
2 Timakova St., Novosibirsk, 630060
Phone: + 7(383)274-94-97
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Review
For citations:
Kim L.B., Putyatina A.N., Russkikh G.S. Effects of Dextrazide on Metabolism of Extracellular Matrix in Mouse Organs during Chronic BCG-Induced Granulomatosis. Tuberculosis and Lung Diseases. 2025;103(3):79-87. (In Russ.) https://doi.org/10.58838/2075-1230-2025-103-3-79-87
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