Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

Han,Kun; Zhang,Yanting; Yang,Zhenwei

doi:10.3892/etm.2019.7207

Cilostazol protects rats against alcohol‑induced hepatic fibrosis via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway

Authors:
- Kun Han
- Yanting Zhang
- Zhenwei Yang
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Affiliations: Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China
Published online on: January 28, 2019 https://doi.org/10.3892/etm.2019.7207
Pages: 2381-2388

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Abstract

Alcohol abuse and chronic alcohol consumption are major causes of alcoholic liver disease worldwide, particularly alcohol‑induced hepatic fibrosis (AHF). Liver fibrosis is an important public health concern because of its high morbidity and mortality. The present study examined the mechanisms and effects of the phosphodiesterase III inhibitor cilostazol on AHF. Rats received alcohol infusions via gavage to induce liver fibrosis and were treated with colchicine (positive control) or cilostazol. The serum alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities and the albumin/globulin (A/G), enzymes and hyaluronic acid (HA), type III precollagen (PC III), laminin (LA), and type IV collagen (IV‑C) levels were measured using commercially available kits. α‑smooth muscle actin (α‑SMA), collagen I and III, transforming growth factor‑β1 (TGF‑β1), connective tissue growth factor (CTGF), adenosine 3',5'‑cyclic monophosphate (cAMP) and exchange protein directly activated by cAMP (Epac) 1/2 expression in liver tissue were measured using western blotting. The results demonstrated that cilostazol significantly increased the serum ADH and ALDH activities and decreased the liver hydroxyproline levels. Cilostazol increased the serum A/G ratio and inhibited the total serum protein, enzymes, HA, PCIII, LA and IV‑C levels. Western blotting revealed that cilostazol effectively decreased liver α‑SMA, collagen I and III, TGF‑β1 and CTGF expression. Cilostazol significantly increased the cAMP and Epac1 levels in hepatic tissue. The present study suggests that cilostazol protects rats against AHF via suppression of TGF‑β1/CTGF activation and the cAMP/Epac1 pathway.

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