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タイトル: | Cilostazol attenuates hepatic stellate cell activation and protects mice against carbon tetrachloride-induced liver fibrosis. |
著者: | Saito, Shunichi Hata, Koichiro https://orcid.org/0000-0002-3609-6396 (unconfirmed) Iwaisako, Keiko Yanagida, Atsuko Takeiri, Masatoshi Tanaka, Hirokazu Kageyama, Shoichi Hirao, Hirofumi Ikeda, Kazuo Asagiri, Masataka Uemoto, Shinji |
著者名の別形: | 秦, 浩一郎 |
キーワード: | carbon tetrachloride cilostazol hepatic stellate cells liver fibrosis phosphodiesterase-3 inhibitor platelet-derived growth factor |
発行日: | 30-Jun-2013 |
出版者: | wiley |
誌名: | Hepatology research |
巻: | 44 |
号: | 4 |
開始ページ: | 460 |
終了ページ: | 473 |
抄録: | [Aim]Liver fibrosis is a common pathway leading to cirrhosis. Cilostazol, a clinically available oral phosphodiesterase-3 inhibitor, has been shown to have antifibrotic potential in experimental non-alcoholic fatty liver disease. However, the detailed mechanisms of the antifibrotic effect and its efficacy in a different experimental model remain elusive. [Methods] Male C57BL/6J mice were assigned to five groups: mice fed a normal diet (groups 1 and 2); 0.1% or 0.3% cilostazol-containing diet (groups 3 and 4, respectively); and 0.125% clopidogrel-containing diet (group 5). Two weeks after feeding, groups 2–5 were intraperitoneally administered carbon tetrachloride (CCl4) twice a week for 6 weeks, while group 1 was treated with the vehicle alone. To investigate the effects of cilostazol on hepatic cells, in vitro studies were conducted using primary hepatic stellate cells (HSC), Kupffer cells and hepatocytes with cilostazol supplementation. [Results] Sirius red staining revealed that groups 3 and 4 exhibited a lesser fibrotic area (2.49 ± 0.43% and 2.31 ± 0.30%, respectively) than group 2 (3.17 ± 0.67%, P < 0.05 and P < 0.001, respectively). In vitro studies showed cilostazol dose-dependently suppressed HSC activation (assessed by morphological change, cell proliferation, and the expression of HSC activation markers), suggesting the therapeutic effect of cilostazol is mediated by its direct action on HSC. [Conclusion] Cilostazol could alleviate CCl4-induced hepatic fibrogenesis in vivo, presumably due, at least partly, to its direct effect to suppress HSC activation. Given its clinical availability and safety, it may be a novel therapeutic intervention for chronic liver diseases. |
著作権等: | This is the peer reviewed version of the following article: Saito, S., Hata, K., Iwaisako, K., Yanagida, A., Takeiri, M., Tanaka, H., Kageyama, S., Hirao, H., Ikeda, K., Asagiri, M. and Uemoto, S. (2014), Cilostazol attenuates hepatic stellate cell activation and protects mice against carbon tetrachloride-induced liver fibrosis. Hepatology Research, 44: 460–473, which has been published in final form at http://dx.doi.org/10.1111/hepr.12140. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/198831 |
DOI(出版社版): | 10.1111/hepr.12140 |
PubMed ID: | 23607402 |
出現コレクション: | 学術雑誌掲載論文等 |
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