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Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease
  1. Koji Fujita (t046043e{at}yokohama-cu.ac.jp)
  1. Yokohama-City University School of Medicine, Japan
    1. Yuichi Nozaki (nzaki-y{at}fukuhp.yokohama-cu.ac.jp)
    1. Yokohama-City University School of Medicine, Japan
      1. Masato Yoneda (yoneda{at}med.yokohama-cu.ac.jp)
      1. Yokohama-City University School of Medicine, Japan
        1. Koichiro Wada (kwada{at}dent.osaka-u.ac.jp)
        1. Osaka University Graduate School of Dentistry, Japan
          1. Hiroki Endo (t066011b{at}yokohama-cu.ac.jp)
          1. Yokohama-City University School of Medicine, Japan
            1. Hirokazu Takahashi (hirokazu{at}med.yokohama-cu.ac.jp)
            1. Yokohama-City University School of Medicine, Japan
              1. Tomoyuki Iwasaki
              1. Yokohama-City University School of Medicine, Japan
                1. Masahiko Inamori (inamorim{at}med.yokohama-cu.ac.jp)
                1. Yokohama-City University School of Medicine, Japan
                  1. Yasunobu Abe (a0121{at}yokohama-cu.ac.jp)
                  1. Yokohama-City University School of Medicine, Japan
                    1. Hiroyuki Kirikoshi (hkirikos{at}med.yokohama-cu.ac.jp)
                    1. Yokohama-City University School of Medicine, Japan
                      1. Noritoshi Kobayashi (norikoba{at}yokohama-cu.ac.jp)
                      1. Yokohama-City University School of Medicine, Japan
                        1. Kensuke Kubota (kubotak{at}yokohama-cu.ac.jp)
                        1. Yokohama-City University School of Medicine, Japan
                          1. Satoru Saito (ssai1423{at}yokohama-cu.ac.jp)
                          1. Yokohama-City University School of Medicine, Japan
                            1. Yoji Nagashima (ynagas{at}med.yokohama-cu.ac.jp)
                            1. Yokohama-City University School of Medicine, Japan
                              1. Atsushi Nakajima (nakajima-tky{at}umin.ac.jp)
                              1. Yokohama-City University School of Medicine, Japan

                                Abstract

                                Objective: No effective drugs have been developed until 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, we propose a novel concept for the treatment of NAFLD.

                                Methods: Fisher 344 male rats were given a choline-deficient, l-amino acid-defined (CDAA) diet or 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 the 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 MAP kinase activation induced by oxidative stress and platelet-derived growth factor (PDGF) 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.

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