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.