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Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl 4
Author(s) -
Chávez Enrique,
CastroSánchez Luis,
Shibayama Mineko,
Tsutsumi Victor,
Pérez Salazar Eduardo,
Moreno Mario G.,
Muriel Pablo
Publication year - 2012
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1638
Subject(s) - pharmacology , ibuprofen , lipid peroxidation , chemistry , glutathione , cyclooxygenase , oxidative stress , ccl4 , fibrosis , liver injury , inflammation , enzyme , medicine , carbon tetrachloride , biochemistry , organic chemistry
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are drugs used primarily to treat inflammation, pain and fever. Their main mechanism of action is cyclooxygenase (COX) inhibition, and this enzyme has been linked to hepatotoxicity. The association of COX and liver injury has been, in part, due to the presence of COX‐2 isoform in damaged liver and the possible induction of this enzyme by profibrotic molecules like Transforming Growth Factor‐ β (TGF‐ β ). The aim of this work was to evaluate the effects of two of the most used NSAIDs, acetyl salicylic acid (ASA) and ibuprofen (IBP), on experimental liver fibrosis. We formed experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl 4 (0.4 g kg −1 , i.p., three times per week, for 8 weeks) administration, and CCl 4 plus ASA (100 mg kg −1 , p.o., daily) or IBP (30 mg kg −1 , p.o., daily). Both drugs showed important antifibrotic properties. They inhibited COX‐2 activity, prevented oxidative stress measured as lipid peroxidation and glutathione content, and ASA inhibited partially and IBP totally increased TGF‐ β expression and collagen content. ASA and IBP prevented translocation of NF κ B to the nucleus and, interestingly, ASA induced MMP‐2 and MMP‐13 whereas IBP induced MMP‐2, MMP‐9 and MMP‐13. As a whole, these effects explain the beneficial effects of ASA and IBP on experimental liver fibrosis. Copyright © 2011 John Wiley & Sons, Ltd.