Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl4

✍ Scribed by Enrique Chávez; Luis Castro-Sánchez; Mineko Shibayama; Victor Tsutsumi; Eduardo Pérez Salazar; Mario G. Moreno; Pablo Muriel

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 865 KB
• Volume: 32
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1638

✦ Synopsis

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 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.