title: Reduction of periductal fibrosis in liver fluke-infected hamsters after long-term curcumin treatment.
abstract: 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.
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. psomec@kku.ac.th
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
authors.forename: Suksanti
authors.initials: S
authors.lastname: Prakobwong
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: Porntip
authors.initials: P
authors.lastname: Pinlaor
authors.forename: Umawadee
authors.initials: U
authors.lastname: Laothong
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D006224:Cricetinae; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000096:biosynthesis; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009889:Opisthorchiasis / Q000188:drug therapy*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000199:Actins; D053583:Interleukin-1beta; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020782:Matrix Metalloproteinases; D003474:Curcumin; D006909:Hydroxyproline