Abstract
The dynamics of intracellular reorganization of rat hepatocytes was studied after a single injection of doxorubicin. The hepatocyte population is presented by three main ultrastructural phenotypes. Quantitative ratio between these phenotypes changed during the development of anthracycline hepatopathy. Ultrastructural changes in hepatocytes are determined by the development of the regeneratory plastic insufficiency characterized by segregation and annular reorganization of the nucleoli, destruction of the mitochondrial compartment, and the resultant lipid infiltration of the cytoplasm, as well as intensification of autophagocytosis, all these changes persisting for a long time. This was paralleled (in some hepatocytes) by signs of intracellular regeneration and compensatory adaptive restructuring manifesting in pronounced hyperplasia of the Golgi complex and remodeling of the biliary and sinusoidal hepatocyte poles reflecting activation of exo-, endo, and transcytosis. Disproportional changes in the volume density of the granular and agranular endoplasmic reticulum indicate transitory predominance of protein-producing processes over detoxifying ones in the hepatocyte population.
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References
A. F. Blyuger, V. K. Zaltsmane, and O. Ya. Kartashova, Ultrastructural Pathology of the Liver [in Russian], Riga (1989).
E. D. Gol’dberg, T. I. Fomina, T. V. Vetoshkina, et al., Byull Eksp. Biol. Med., 126, No. 11, 561–565 (1998).
E. L. Lushnikova, L. M. Nepomnyashchikh, M. G. Klinnikova, and O. P. Molodykh, Morfologiya, 128, No. 4, 81–84 (2005).
O. P. Molodykh, E. L. Lushnikova, M. G. Klinnikova, and L. M. Nepomnyashchikh, Byull. Eksp. Biol. Med., 141, No. 5, 579–585 (2006).
E. S. Snigirevskaya, Yu. Ya. Sokolova, and Ya. Yu. Komissarchik, Tsitologiya, 48, No. 4, 283–307 (2006).
A. P. Shiryaeva, E. V. Baidyuk, A. V. Arkadyeva, et al., Ibid., 49, No. 2, 125–132 (2007).
S. Chitturi and J. George, Semin. Liver Dis., 22, No. 2, 169–183 (2002).
L. D. DeLeve, H. M. Shulman, and G. B. McDonald, Ibid., 22, No. 1, 27–42 (2002).
S. N. Hilmer, V. C. Cogger, M. Muller, and D. G. Le Couteur, Drug Metab. Dispos., 32, No. 8, 794–799 (2004).
H. Jaeschke, G. J. Gores, A. I. Cederbaum, et al., Toxicol. Sci., 65, No. 2, 166–176 (2002).
W. M. Lee, N. Engl. J. Med., 349, No. 5, 474–485 (2003).
V. J. Navarro and J. R. Senior, Ibid., 354, No. 7, 731–739 (2006).
G. Minotti, M. Parlani, E. Salvatorelli, et al., Brit. J. Pharmacol., 134, No. 6, 1271–1278 (2001).
B. K. Park, N. R. Kitteringham, J. L. Maggs, et al., Annu. Rev. Pharmacol. Toxicol., 45, 177–202 (2005).
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 10, pp. 464–472, October, 2007
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Molodykh, O.P., Lushnikova, E.L., Klinnikova, M.G. et al. Intracellular reorganization of hepatocytes during doxorubicin treatment. Bull Exp Biol Med 144, 580–587 (2007). https://doi.org/10.1007/s10517-007-0382-6
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DOI: https://doi.org/10.1007/s10517-007-0382-6