Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease

被引：110

作者：

Fujita, K. ^{[1
]}

Nozaki, Y. ^{[1
]}

Wada, K. ^{[2
]}

Yoneda, M. ^{[1
]}

Endo, H. ^{[1
]}

Takahashi, H. ^{[1
]}

Iwasaki, T. ^{[3
]}

Inamori, M. ^{[1
]}

Abe, Y. ^{[1
]}

Kobayashi, N. ^{[1
]}

Kirikoshi, H. ^{[1
]}

Kubota, K. ^{[1
]}

Saito, S. ^{[1
]}

Nagashima, Y. ^{[4
]}

Nakajima, A. ^{[1
]}

机构：

[1] Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Osaka Univ, Dept Pharmacol, Grad Sch Dent, Osaka, Japan

[3] Yokohama City Univ, Grad Sch Med, Div Endocrinol & Metab, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[4] Yokohama City Univ, Dept Mol Pathol, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

来源：

GUT | 2008年 / 57卷 / 11期

关键词：

D O I：

10.1136/gut.2007.144550

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective: No effective drugs have been developed to date to prevent or treat non-alcoholic fatty liver disease ( NAFLD), although diet modification and exercise to improve obesity have been attempted. Therefore, development of a novel drug/strategy to treat NAFLD is urgently needed. In the present study, a novel concept is proposed for the treatment of NAFLD. Methods: Fisher 344 male rats were given a choline-deficient, L-amino acid-defined ( CDAA) diet or a high-fat high-calorie ( HF/HC) diet with or without the antiplatelet agents, aspirin, ticlopidine or cilostazol for 16 weeks. Liver steatosis, inflammation and fibrosis, and the possible mechanisms involved were investigated. Results: All three antiplatelet drugs, namely aspirin, ticlopidine and cilostazol, significantly attenuated liver steatosis, inflammation and fibrosis in the CDAA diet group. Of the three agents, cilostazol was the most effective, and the drug also suppressed HF/HC diet-induced liver steatosis. Cilostazol appeared to exert its beneficial effect against NAFLD by suppressing mitogen-activated protein kinase activation induced by oxidative stress and platelet-derived growth factor via intercepting signal transduction from Akt to c-Raf. Conclusion: Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.

引用

页码：1583 / 1591

页数：9

共 36 条

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