{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:20:33Z","timestamp":1792592433006,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"4b","license":[{"start":{"date-parts":[[2012,1,26]],"date-time":"2012-01-26T00:00:00Z","timestamp":1327536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,2,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND PURPOSE<\/jats:title><jats:p>Oxidative stress plays a critical role in liver fibrogenesis. Reactive oxygen species (ROS) stimulate hepatic stellate cells (HSCs), and ROS\u2010mediated increases in calcium influx further increase ROS production. Azelnidipine is a calcium blocker that has been shown to have antioxidant effects in endothelial cells and cardiomyocytes. Therefore, we evaluated the anti\u2010fibrotic and antioxidative effects of azelnidipine on liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>We used TGF\u2010\u03b21\u2010activated LX\u20102 cells (a human HSC line) and mouse models of fibrosis induced by treatment with either carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) or thioacetamide (TAA).<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Azelnidipine inhibited TGF\u2010\u03b21 and angiotensin II (Ang II)\u2010activated \u03b11(I) collagen mRNA expression in HSCs. Furthermore, TGF\u2010\u03b21\u2010 and Ang II\u2010induced oxidative stress and TGF\u2010\u03b21\u2010induced p38 and JNK phosphorylation were reduced in HSCs treated with azelnidipine. Azelnidipine significantly decreased inflammatory cell infiltration, pro\u2010fibrotic gene expressions, HSC activation, lipid peroxidation, oxidative DNA damage and fibrosis in the livers of CCl<jats:sub>4<\/jats:sub>\u2010 or TAA\u2010treated mice. Finally, azelnidipine prevented a decrease in the expression of some antioxidant enzymes and accelerated regression of liver fibrosis in CCl<jats:sub>4<\/jats:sub>\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS AND IMPLICATIONS<\/jats:title><jats:p>Azelnidipine inhibited TGF\u2010\u03b21\u2010 and Ang II\u2010induced HSC activation<jats:italic>in vitro<\/jats:italic>and attenuated CCl<jats:sub>4<\/jats:sub>\u2010 and TAA\u2010induced liver fibrosis, and it accelerated regression of CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis in mice. The anti\u2010fibrotic mechanism of azelnidipine against CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis in mice may have been due an increased level of antioxidant defence. As azelnidipine is widely used in clinical practice without serious adverse effects, it may provide an effective new strategy for anti\u2010fibrotic therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2011.01599.x","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T14:53:22Z","timestamp":1311692002000},"page":"1173-1187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Azelnidipine is a calcium blocker that attenuates liver fibrosis and may increase antioxidant 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