Acta Tropica 111 (2009) 181–191 Contents lists available at ScienceDirect Acta Tropica journal homepage: www.elsevier.com/locate/actatropica Effect of praziquantel treatment on the expression of matrix metalloproteinases in relation to tissue resorption during fibrosis in hamsters with acute and chronic Opisthorchis viverrini infection Somchai Pinlaor a,d,∗ , Suksanti Prakobwong a,d , Thidarut Boonmars a,d , Chaisiri Wongkham b,d , Porntip Pinlaor c,d , Yusuke Hiraku e a Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand b Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand c Department of Clinical Microbiology, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002, Thailand d Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand e Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan article info Article history: Received 23 October 2008 Received in revised form 20 April 2009 Accepted 29 April 2009 Available online 7 May 2009 Keywords: Opisthorchis viverrini Praziquantel Peribiliary fibrosis Matrix metalloproteinase Tissue inhibitor of metalloproteinase Cytokines Fibrolysis abstract Praziquantel has been used for the treatment of diseases caused by infection with various parasites. Praziquantel treatment in Opisthorchis viverrini-infected patients reduces the hepatobiliary fibrosis due to tissue resorption, however, some fibroses are irreversible. To clarify the effect of praziquantel treatment on hepatobiliary fibrosis, we examined the expression of matrix metalloproteinases (MMPs) in relation to fibrolysis on praziquantel-treated hamsters after O. viverrini acute infection (AI) for 21 days and chronic infection (CI) for 4 months. The reduction rate of hydroxyproline content in the livers of the AI group with 6-month praziquantel treatment (71%) was higher than that of corresponding praziquantel-treated CI group (13%), similar to the decrease in the thickness of peribiliary fibrosis. Hepatic mRNA levels of collagen I significantly decreased compared with untreated control after praziquantel treatment both in AI and CI groups. Expression of collagen III significantly decreased in the AI group but unchanged in the CI group. MMP-9 and MMP-13 (except 3 months in CI group) levels significantly decreased in both groups. Notably, expression of MMP-7 level increased at 1 and 6 months in both AI and CI groups, respectively. MMP-2 level did not change in both groups. Gelatinase activity of MMPs-2 and -9 was associated with their transcriptional levels. Tissue inhibitors of MMP (TIMP)-1 and TIMP-2 significantly decreased in the AI group, whereas TIMP-1 levels did not change and TIMP-2 level was significantly increased in CI group. Praziquantel treatment increased the expression of TNF- in both groups, suggesting an association with MMP-7 expression. TGF- expression was significantly increased only in the CI group indicating its may involve in TIMPs expression. These results suggest that in animals with chronic O. viverrini infection, praziquantel treatment induces the expression of TGF-, and TIMPs and resultant inhibition of MMP activity, leading to slow resorption of hepatic fibrosis. © 2009 Published by Elsevier B.V. 1. Introduction Chronic infection with Opisthorchis viverrini is the major risk fac- tor for cholangiocarcinoma (CCA) development (IARC, 1994) and is still a major health problem in northeastern Thailand. O. viverrini infection causes opisthorchiasis, where 18.5% of people (3.8 mil- lion) are estimated to be infected (Jongsuksuntigul and Imsomboon, 2003). The severity of the disease depends on the duration and the ∗ Corresponding author at: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Tel.: +66 43 348 387; fax: +66 43 202 475. E-mail addresses: psomec@kku.ac.th, mrsomchaip@yahoo.com (S. Pinlaor). frequency of infection (IARC, 1994). An experimental opisthorchi- asis shows similar pathological changes to the human disease (Bhamarapravati et al., 1978; Harinasuta et al., 1984). Periductal fibrosis is the most prominent during chronic infection in ham- sters infected with O. viverrini (Pinlaor et al., 2004), and it persists after one-week of praziquantel treatment (Pinlaor et al., 2006). A study in the community shows the improvement of biliary tract abnormalities following praziquantel treatment, but some abnor- malities are not affected by the treatment (Mairiang et al., 1993). The irreversible fibrosis may cause the formation of biliary sludge and primary sclerosing cholangitis, leading to CCA development. An imbalance between matrix metalloproteinases (MMPs) and the tissue inhibitor of MMPs (TIMPs) expression has been impli- cated as a possible mechanism of the severity of the disease by 0001-706X/$ – see front matter © 2009 Published by Elsevier B.V. doi:10.1016/j.actatropica.2009.04.011