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


CONCLUSIONS
Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.
Fujita
K
K
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Nozaki
Y
Y
Wada
K
K
Yoneda
M
M
Endo
H
H
Takahashi
H
H
Iwasaki
T
T
Inamori
M
M
Abe
Y
Y
Kobayashi
N
N
Kirikoshi
H
H
Kubota
K
K
Saito
S
S
Nagashima
Y
Y
Nakajima
A
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism; D002796:Choline Deficiency / Q000378:metabolism; D000077407:Cilostazol; D004041:Dietary Fats / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013777:Tetrazoles / Q000627:therapeutic use*; D013988:Ticlopidine / Q000627:therapeutic use*; D016896:Treatment Outcome
D004041:Dietary Fats; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D002784:Cholesterol; D000410:Alanine Transaminase; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin