Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction
Autor: | Jorge A. Mendoza-Pérez, María Isabel Sánchez-Reus, Jaime Esquivel-Soto, David Andrés, José Gutiérrez-Salinas, Tomás Fregoso-Aguilar, Eduardo Madrigal-Santillán, María Cascales, Carmen Valadez-Vega, Mirandeli Bautista, José A. Morales-González |
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Rok vydání: | 2011 |
Předmět: |
Male
Cyclin E Necrosis Cyclin D Pharmaceutical Science Gadolinium Thioacetamide Analytical Chemistry gadolinium chloride chemistry.chemical_compound Drug Discovery Liver injury Biología molecular thioacetamide hepatotoxicity Cell cycle Liver regeneration Liver Biochemistry Chemistry (miscellaneous) Molecular Medicine cell cycle Chemical and Drug Induced Liver Injury medicine.symptom cyclins Bioquímica Biology Article lcsh:QD241-441 Cyclin D1 lcsh:Organic chemistry Proliferating Cell Nuclear Antigen medicine Animals kupffer cells Rats Wistar Physical and Theoretical Chemistry Cell Proliferation Organic Chemistry Cell Cycle Checkpoints medicine.disease Molecular biology Liver Regeneration Rats chemistry biology.protein |
Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname Molecules, Vol 16, Iss 10, Pp 8319-8331 (2011) Molecules; Volume 16; Issue 10; Pages: 8319-8331 Molecules |
ISSN: | 1420-3049 |
DOI: | 10.3390/molecules16108319 |
Popis: | 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. |
Databáze: | OpenAIRE |
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