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

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-α in both groups, suggesting an association with MMP-7 expression. TGF-β 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-β, and TIMPs and resultant inhibition of MMP activity, leading to slow resorption of hepatic fibrosis.