Chronic infection with the liver fluke, Opisthorchis viverrini, induces advanced periductal
fibrosis and is a relative risk factor for cholangiocarcinoma in Southeastern Asia.
We examined the reducing effect of curcumin on hepatobiliary fibrosis using O. viverrini-infected
hamsters supplemented with dietary 1% curcumin (w/w) as an animal model. The expression
profile of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs),
cytokines, and collagens was assessed in relation to liver fibrosis. Histopathological
studies revealed that curcumin had no effect on fibrosis at the short-term infection
(21 days and 1 month); however, peribiliary fibrosis was significantly reduced after
the long-term curcumin treatment for 3 months, compared to the untreated group. Expression
of alpha-smooth muscle actin was associated with the reduction of liver fibrosis.
A decrease in hepatic hydroxyproline level and mRNA expression of collagen I and III
supported the reduction of fibrosis. The expression of TIMP-1, TIMP-2, and tumor necrosis
factor-alpha genes was also decreased after curcumin treatment. In contrast, curcumin
increased mRNA expression of MMP-13, MMP-7 (at 6 months), interleukin-1 beta, and
transforming growth factor beta, implying that increased MMPs activity contributes
to extracellular matrix degradation. These results suggest that curcumin reduces periductal
fibrosis after long-term treatment by tissue resorption via inhibition of TIMPs expression
and enhancement of MMPs expression mediated by cytokines. In conclusion, curcumin
may serve as a promising nutraceutical agent exerting antifibrotic effect in O. viverrini-infected
patients and contribute to cholangiocarcinoma prevention.
(c) 2010 Elsevier B.V. All rights reserved.