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Beneficial effects of cilostazol on liver injury induced by common bile duct ligation in rats: Role of SIRT 1 signaling pathway
Author(s) -
Kabil Soad L.
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13004
Subject(s) - cilostazol , pharmacology , liver injury , downregulation and upregulation , medicine , antioxidant , bile duct , sirtuin 1 , inflammation , chemistry , endocrinology , aspirin , biochemistry , gene
Summary Liver fibrosis is a health challenge requiring alternative therapeutic approaches. Cilostazol is a selective phosphodiesterase‐3 inhibitor and possesses antioxidant, anti‐inflammatory and antifibrotic properties. Sirtuin 1 ( SIRT 1) is a member of the silent information regulator 2 family. Cilostazol upregulates SIRT 1 expression. Cilostazol protects against the cholestatic liver insults caused by bile duct obstruction. Involvement of SIRT 1 pathway in this protective effect has not been studied yet. So, we hypothesized that SIRT 1 signaling may have a role in cilostazol protective effects against bile duct ligation‐induced liver damages. Rats were subjected to common bile duct ligation then treated with cilostazol (9 mg/kg or 27 mg/kg) in the presence or absence of specific SIRT 1 inhibitor EX 527. Cilostazol improved liver function, reduced inflammation, enhanced antioxidant status, ameliorated cholestatic liver injury and upregulated hepatic SIRT 1. However, these protective effects were abrogated by EX 527, suggesting that SIRT 1 signaling may have a role in these effects. In conclusion, cilostazol in a dose‐dependent way produced hepatoprotective effects via anti‐inflammatory, antioxidant, antifibrotic effects which were mediated, in part, through SIRT 1 upregulation.