Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat

被引:47
作者
Yoshiji H. [1 ]
Noguchi R. [1 ]
Ikenaka Y. [1 ]
Namisaki T. [1 ]
Kitade M. [1 ]
Kaji K. [1 ]
Shirai Y. [1 ]
Yoshii J. [1 ]
Yanase K. [1 ]
Yamazaki M. [1 ]
Tsujimoto T. [1 ]
Kawaratani H. [1 ]
Akahane T. [1 ]
Aihara Y. [1 ]
Fukui H. [1 ]
机构
[1] Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522
关键词
Insulin Resistance; NASH; Losartan; Rosiglitazone; Pioglitazone;
D O I
10.1186/1756-0500-2-70
中图分类号
学科分类号
摘要
Background. Apart from simple steatosis, the non-alcoholic steatohepatitis (NASH) can progress into liver fibrosis and cirrhosis. To date, however, no widely accepted therapeutic modalities have been established against NASH in the clinical practice. To find out promising new therapeutic agents, it is important to employ an appropriate experimental model of NASH, such as association with insulin resistance. Findings. In the current study, we found that losartan, a clinically used angiotensin-II type 1 receptor blocker, significantly attenuated a choline-deficient L-amino acid-defined (CDAA) diet-induced steatohepatitis in obese diabetic- and insulin resistance- associated Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The transforming growth factor-beta, a well-known major fibrogenic cytokine, was also suppressed in a similar magnitude to that of the fibrosis area. Noteworthy was the finding that these inhibitory effects were achieved even at a clinically comparable low dose. Conclusion. Since losartan is widely used without serious side effects in the clinical practice, this agent may be an effective new therapeutic strategy against NASH. © 2009 Yoshiji et al.
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共 10 条
[1]  
Reid A.E., Nonalcoholic steatohepatitis, Gastroenterology, 121, 3, pp. 710-723, (2001)
[2]  
Marrero J.A., Fontana R.J., Su G.L., Conjeevaram H.S., Emick D.M., Lok A.S., NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States, Hepatology, 36, 6, pp. 1349-1354, (2002)
[3]  
Vuppalanchi R., Chalasani N., Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management, Hepatology, 49, 1, pp. 306-317, (2009)
[4]  
Ratziu V., Giral P., Jacqueminet S., Charlotte F., Hartemann-Heurtier A., Serfaty L., Podevin P., Lacorte J.M., Bernhardt C., Bruckert E., Et al., Rosiglitazone for nonalcoholic steatohepatitis: One-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial, Gastroenterology, 135, 1, pp. 100-110, (2008)
[5]  
Liu Z., The renin-angiotensin system and insulin resistance, Current Diabetes Reports, 7, 1, pp. 34-42, (2007)
[6]  
Yoshiji H., Kuriyama S., Fukui H., Blockade of renin-angiotensin system in antifibrotic therapy, J Gastroenterol Hepatol, 22, SUPPL 1, pp. 1993-95, (2007)
[7]  
Hirose A., Ono M., Saibara T., Nozaki Y., Masuda K., Yoshioka A., Takahashi M., Akisawa N., Iwasaki S., Oben J.A., Onishi S., Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis, Hepatology, 45, 6, pp. 1375-1381, (2007)
[8]  
Yoshiji H., Yoshii J., Ikenaka Y., Noguchi R., Tsujinoue H., Nakatani T., Imazu H., Yanase K., Kuriyama S., Fukui H., Inhibition of renin-angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats, J Hepatol, 37, 1, pp. 22-30, (2002)
[9]  
Remuzzi A., Perico N., Amuchastegui C.S., Malanchini B., Mazerska M., Battaglia C., Bertani T., Remuzzi G., Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes, J Am Soc Nephrol, 4, 1, pp. 40-49, (1993)
[10]  
Yokohama S., Yoneda M., Haneda M., Okamoto S., Okada M., Aso K., Hasegawa T., Tokusashi Y., Miyokawa N., Nakamura K., Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis, Hepatology, 40, 5, pp. 1222-1225, (2004)