Hepatobiliary changes, antibody response, and alteration of liver enzymes in hamsters re-infected with Opisthorchis viverrini

Pinlaor, Somchai; Sripa, Banchob; Sithithaworn, Paiboon; Yongvanit, Puangrat

doi:10.1016/j.exppara.2004.07.007

Cited by 39 publications

(31 citation statements)

References 33 publications

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“…18 Experimental models using hamsters demonstrated that OV-associated antigens induced strong local inflammatory response, 32 and re-infection with OV resulted in early inflammatory changes of the liver and alterations of liver enzymes. 33 Taken together, induction of genotoxic stress by carcinogens, unknown substance(s) produced by OV, or chronic inflammation attributable to the OV infection may play a crucial role in the carcinogenesis of Thai ICCs. Polymorphisms in UDP-glucuronosyltransferases and sulfotransferases were reportedly linked with the risk of ER-negative breast cancer tumors.…”

Section: Discussionmentioning

confidence: 99%

Comparison of gene expression profiles betweenOpisthorchis viverriniandnon-Opisthorchis viverriniassociated human intrahepatic cholangiocarcinoma

et al. 2006

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Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in the liver, and its incidence is highest in the northeastern part of Thailand. ICCs in this region are known to be associated with infection with liver flukes, particularly Opisthorchis viverrini (OV), as well as nitrosamines from food. To clarify molecular mechanisms of ICC associated with or without liver flukes, we analyzed gene expression profiles of OV-associated ICCs from 20 Thai patients and compared their profiles with those of 20 Japanese ICCs that were not associated with OV, by means of laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 77 commonly upregulated genes and 325 commonly downregulated genes in the two ICC groups. Unsupervised hierarchical cluster analysis separated the 40 ICCs into two major branches almost completely according to the fluke status. The putative signature of OV-associated ICC exhibited elevated expression of genes involved in xenobiotic metabolism (UGT2B11, UGT1A10, CHST4, SULT1C1), whereas that of non-OV-associated ICC represented enhanced expression of genes related to growth factor signaling (TGFBI, PGF, IGFBP1, IGFBP3). Additional random permutation tests identified a total of 49 genes whose expression levels were significantly different between the two groups. We also identified genes associated with macroscopic type of ICCs. In conclusion, these data may not only contribute to clarification of common and OV-specific mechanisms underlying ICC, but also may serve as a starting point for the identification of novel diagnostic markers or therapeutic targets for the disease.

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Section: Discussionmentioning

confidence: 99%

Comparison of gene expression profiles betweenOpisthorchis viverriniandnon-Opisthorchis viverriniassociated human intrahepatic cholangiocarcinoma

et al. 2006

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“…Fibrosis replaces the periportal inflammation over time (38) . Re-infection, which is common and often continual in endemic areas, results in more severe inflammation, and accelerated fibrosis (39) . Induction of fibrosis after inflammation is an important part of the pathway of pathological changes that lead to cholangiocarcinoma (40) .…”

Section: Cholangiocarcinomamentioning

confidence: 99%

Human liver flukes

Harrington

Lamberton

McGregor

2017

The Lancet Gastroenterology & Hepatology

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“…We isolated metacercariae of OV from cyprinoid fish as described previously. 24 Hamsters were fed with 50 metacercariae of OV by intragastric intubation. Animals were sacrificed on days 14 or 30.…”

Section: Animal Experimentsmentioning

confidence: 99%

iNOS‐dependent DNA damage via NF‐κB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel

Pinlaor

Hiraku

Yongvanit

et al. 2006

Intl Journal of Cancer

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Inflammation-mediated DNA damage triggered by Opisthorchis viverrini (OV) infection is a major risk factor of cholangiocarcinoma (CCA). We have recently reported that nitrative and oxidative DNA damage participates in CCA development caused by repeated infection with OV [Pinlaor et al., Carcinogenesis 2004; 25:1535-42]. Therefore, to clarify the preventive effect of the antihelminthic drug praziquantel against cholangiocarcinogenesis, we assessed the effect of this drug on nitrative and oxidative DNA damage, including the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxodG), and the expression of inducible nitric oxide synthase (iNOS) by immunohistochemistry in OV-infected hamsters. We also examined the expression of nuclear factor-jB (NF-jB), which functions as a tumor promoter in inflammation-associated cancer. Our results showed that although 1-week treatment with praziquantel did not kill parasites completely in hamsters on days 14 and 30, this drug dramatically reduced inflammatory cell infiltration. Double immunofluorescence staining showed that drug treatment almost completely diminished OV-induced 8-nitroguanine and 8-oxodG formation in bile duct epithelial cells. Quantitative analysis using an electrochemical detector coupled to HPLC revealed that 8-oxodG level in the liver of OV-infected hamsters was significantly decreased by drug treatment (p<0.05). Western blotting and immunohistochemistry revealed that the expression of NF-jB and iNOS in bile duct epithelium was reduced by drug treatment. The amount of nitrate plus nitrite in the liver and plasma was significantly decreased after drug treatment. It is concluded that praziquantel can exhibit a preventive effect against OV-induced cholangiocarcinoma by inhibiting iNOS-dependent DNA damage through not only elimination of parasites but also a potential antiinflammatory effect. ' 2006 Wiley-Liss, Inc.Key words: Opisthorchis viverrini; cholangiocarcinoma; praziquantel; DNA damage; 8-nitroguanine; 8-oxo-7, 8-dihydro-2 0 -deoxyguanosine; inducible nitric oxide synthase; nuclear factor-jB; inflammation Opisthorchiasis viverrini (OV) infection is the major risk factor of cholangiocarcinoma (CCA) development.1,2 OV infection and CCA development occur at high incidence in northeastern Thailand.2,3 The antihelminthic drug praziquantel has been used for the treatment of parasite infection, including liver fluke such as OV. 4 The cure rate of a single dose of praziquantel for liver fluke treatment was more than 90%. 4 However, although praziquantel appears to interfere with calcium homeostasis and causes flaccid paralysis in adult flukes, its mode of action is still not clearly understood.5 It is still a matter of debate whether the therapeutic effect of praziquantel is attributed to its specific antiparasitic effect and/or antiinflammatory effect.5,6 Accumulation of evidence verifies that DNA damage is believed to be linked between inflammation and carcinogenesis. [7][8][9] Reactive nitrogen species can mediate the formation of 8-nitr...

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Hepatobiliary changes, antibody response, and alteration of liver enzymes in hamsters re-infected with Opisthorchis viverrini

Cited by 39 publications

References 33 publications

Comparison of gene expression profiles betweenOpisthorchis viverriniandnon-Opisthorchis viverriniassociated human intrahepatic cholangiocarcinoma

Comparison of gene expression profiles betweenOpisthorchis viverriniandnon-Opisthorchis viverriniassociated human intrahepatic cholangiocarcinoma

Human liver flukes

iNOS‐dependent DNA damage via NF‐κB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel

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