title: Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl4.
abstract: 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 CCl4 (0.4 g kg(-1) , i.p., three times per week, for 8 weeks) administration, and CCl4 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 NFκB 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.
authors.affiliation: Departamento de Farmacología, Cinvestav-IPN, Apdo Postal 14-740, México, 07000, D. F. México.
authors.forename: Enrique
authors.initials: E
authors.lastname: Chávez
authors.forename: Luis
authors.initials: L
authors.lastname: Castro-Sánchez
authors.forename: Mineko
authors.initials: M
authors.lastname: Shibayama
authors.forename: Victor
authors.initials: V
authors.lastname: Tsutsumi
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez Salazar
authors.forename: Mario G
authors.initials: MG
authors.lastname: Moreno
authors.forename: Pablo
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D003094:Collagen; D002251:Carbon Tetrachloride; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases; D005978:Glutathione; D001241:Aspirin; D007052:Ibuprofen