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Statement of the Problem: The Morphofunctional state of the liver in diabetes mellitus should be assessed since all metabolic
processes occur in liver; hepatocytes have the insulin-dependent mechanism of glucose metabolism and 40-60% of insulin
is inactivated in liver. The structure of damaged liver tissue and mechanisms of hyperglycemia which cause the damage were
described in many investigations. The assessment of various methods of damaged liver correction was performed. It is known
that hepatic macrophages play key role in tissue injury and repair. However, its effects on regenerative processes in diabetic
liver are not investigated enough. We previously set that the macrophage modulator 3-aminophthalhydrazid (3-APH) activated
anti-inflammatory and antioxidant functions in monocyte-macrophage cells.
The purpose of this study: is to evaluate the impact of macrophages activated by 3-APH on structural defects in diabetic rat
liver.
Methodology: A damaged liver tissue and hepatocyte reparation were studied in alloxan diabetic rats after modulation of
macrophage activity by 3-APH during 30 and 60 days.
Finding: The morphological study of diabetic liver tissue revealed degenerative changes in hepatocytes, inflammatory
processes in the portal and intralobular stroma, microangiopathy and blood circulation disorders. Structural disorders of liver
parenchyma increased at a prolongation of AD up to 60 days. It was found that the administration of 3-APH contributed to
reduction of damage and restoration of normal liver histological structure due to activation of reparative processes.
Conclusion: Thus, macrophage activation in diabetic liver causes increase in hepatocyte activity and compensation of
structural damage in liver tissue. 3-APH is likely to be a promising drug for correction of liver tissue in diabetes due to its
hepato protective effect.
The study is supported by the grant from the Russian Science Foundation, the project ΓΆΒ?Β? 16-15-00039.
Figure 1: a - histological structure of intact rat liver tissue. b ΓΆΒ?Β?diabetic liver tissue (30 days): 1- plethora in central venules, 2-
lymphocytic infiltration of sinusoidal capillary, 3 - degeneration of hepatocytes. c ΓΆΒ?Β? diabetic liver tissue (60 days): 1 - intralobular
necrosis of hepatocytes, 2 - edema, vasodilatation, 3 - desquamation of endothelial of sinusoidal capillaries. d ΓΆΒ?Β?diabetic liver
tissue (60 days) treated by 3-APH: 1 - polyploid hepatocytes, 2 ΓΆΒ?Β? dual-nucleus hepatocytes. Staining by hematoxylin-eosin.
X400.
Recent Publications
ΓΆΒ?ΒΆ Lucchesi A.N. et al. (2013) Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a
mechanism for diabetic chronic liver disease. Acta Cirurgica Brasileira 28.7: 502-508.
ΓΆΒ?ΒΆ Lucchesi A. N., Cassettari L. L., Spadella, C. T. (2015). Alloxan-induced diabetes causes morphological and
ultrastructural changes in rat liver that resemble the natural history of chronic fatty liver disease in humans. Journal
of diabetes research, 2015.
ΓΆΒ?ΒΆ Holt M.P.,Cheng L., Ju C. (2008) Identification and characterization of infiltrating macrophages in acetaminopheninduced
liver injury. Journal of leukocyte biology 84.6: 1410-1421.
ΓΆΒ?ΒΆ Thomas J.A. et al. (2011) Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis,
regeneration, and function. Hepatology 53.6: 2003-2015.
ΓΆΒ?ΒΆ Welt K. et al. (2004) Ultrastructural, immunohistochemical and biochemical investigations of the rat liver exposed
to experimental diabetes und acute hypoxia with and without application of Ginkgo extract. Experimental and
Toxicologic Pathology 55.5: 331-345.
Biography
Irina Danilova, professor, director of the Fundamental Medicine department of the Ural Federal University (UFU), Yekaterinburg, Russia. She is an author of more than 220 scientific publications, “Macrophages Non-immunological Functions” monograph and 5 patents including an EU, USA patent. Irina Gette is a scientific associate of UFU, PhD. She has published 97 papers in reputed journals. Musa Abidov a professor, he is a creator of 3-aminophthalhydrazid. The scope of their research interests has impact on investigation of macrophages during reparative processes in tissue under various pathological states.