Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat
| Autor: | Enrique, Chávez, José, Segovia, Mineko, Shibayama, Victor, Tsutsumi, Paula, Vergara, Luis, Castro-Sánchez, Eduardo Pérez, Salazar, Mario G, Moreno, Pablo, Muriel |
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| Rok vydání: | 2010 |
| Předmět: |
Liver Cirrhosis
Male Time Factors Anti-Inflammatory Agents Antioxidants Transforming Growth Factor beta Malondialdehyde Animals Aspartate Aminotransferases Rats Wistar Carbon Tetrachloride Sulfonamides Cyclooxygenase 2 Inhibitors Alanine Transaminase gamma-Glutamyltransferase Glutathione Rats Disease Models Animal Liver Matrix Metalloproteinase 9 Celecoxib Cyclooxygenase 2 Matrix Metalloproteinase 2 Pyrazoles Collagen Chemical and Drug Induced Liver Injury Glycogen |
| Zdroj: | Liver international : official journal of the International Association for the Study of the Liver. 30(7) |
| ISSN: | 1478-3231 |
| Popis: | Transforming growth factor-beta (TGF-beta) plays a pivotal role in liver fibrosis, because it activates hepatic stellate cells, stimulating extracellular matrix deposition. Cyclooxygenase-2 (COX-2) has been associated with TGF-beta because its inhibition decreases TGF-beta expression and collagen production in some cultured cell types.The aim of this work was to evaluate the ability of celecoxib (a selective COX-2 inhibitor) to prevent and to reverse the liver fibrosis induced by CCl(4).We established experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl(4) administration and CCl(4) plus pharmacological treatment in both prevention and reversion models. We determined: alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, COX and metalloproteinase-2 and -9 activities, lipid peroxidation, glutathione levels, glycogen and collagen content and TGF-beta expression.Celecoxib prevented and aided to the recovery of livers with necrotic and cholestatic damage. Celecoxib exhibited anti-oxidant properties by restoring the redox equilibrium (lipid peroxidation and glutathione levels). Glycogen was decreased by CCl(4), while celecoxib partially prevented and reversed this effect. Celecoxib inhibited COX-2 activity, decreased TGF-beta expression, induced metalloproteinase-2 activity and, consequently, prevented and reversed collagen accumulation.Our findings indicate that celecoxib exerts strong antifibrogenic and fibrolytic effects in the CCl(4) model of cirrhosis. |
| Databáze: | OpenAIRE |
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