Abstract: It is well known that gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA) in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA) were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.
Keywords: gadolinium chloride; kupffer cells; thioacetamide hepatotoxicity; cell cycle; cyclins
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Bautista, M.; Andres, D.; Cascales, M.; Morales-González, J.A.; Sánchez-Reus, M.I.; Madrigal-Santillán, E.; Valadez-Vega, C.; Fregoso-Aguilar, T.; Mendoza-Pérez, J.A.; Gutiérrez-Salinas, J.; Esquivel-Soto, J. Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction. Molecules 2011, 16, 8319-8331.
Bautista M, Andres D, Cascales M, Morales-González JA, Sánchez-Reus MI, Madrigal-Santillán E, Valadez-Vega C, Fregoso-Aguilar T, Mendoza-Pérez JA, Gutiérrez-Salinas J, Esquivel-Soto J. Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction. Molecules. 2011; 16(10):8319-8331.
Bautista, Mirandeli; Andres, David; Cascales, María; Morales-González, José A.; Sánchez-Reus, María Isabel; Madrigal-Santillán, Eduardo; Valadez-Vega, Carmen; Fregoso-Aguilar, Tomas; Mendoza-Pérez, Jorge Alberto; Gutiérrez-Salinas, José; Esquivel-Soto, Jaime. 2011. "Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction." Molecules 16, no. 10: 8319-8331.