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Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat
Author(s) -
Chávez Enrique,
Segovia José,
Shibayama Mineko,
Tsutsumi Victor,
Vergara Paula,
CastroSánchez Luis,
Salazar Eduardo Pérez,
Moreno Mario G.,
Muriel Pablo
Publication year - 2010
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2010.02256.x
Subject(s) - celecoxib , lipid peroxidation , glutathione , chemistry , hepatic stellate cell , carbon tetrachloride , endocrinology , alkaline phosphatase , cyclooxygenase , medicine , glycogen , hydroxyproline , ccl4 , fibrosis , transforming growth factor beta , pharmacology , transforming growth factor , oxidative stress , biochemistry , enzyme , organic chemistry
Background: Transforming growth factor‐β (TGF‐β) 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‐β because its inhibition decreases TGF‐β expression and collagen production in some cultured cell types. Aim: 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 . Methods: 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, γ‐glutamyl transpeptidase, COX and metalloproteinase‐2 and ‐9 activities, lipid peroxidation, glutathione levels, glycogen and collagen content and TGF‐β expression. Results: 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‐β expression, induced metalloproteinase‐2 activity and, consequently, prevented and reversed collagen accumulation. Conclusion: Our findings indicate that celecoxib exerts strong antifibrogenic and fibrolytic effects in the CCl 4 model of cirrhosis.