8-Nitroguanine formation in the liver of hamsters infected with Opisthorchis viverrini

Pinlaor, Somchai; Yongvanit, Puangrat; Hiraku, Yusuke; Ma, Ning; Semba, Reiji; Oikawa, Shinji; Murata, Mariko; Sripa, Banchob; Sithithaworn, Paiboon; Kawanishi, Shosuke

doi:10.1016/j.bbrc.2003.08.039

Cited by 103 publications

(63 citation statements)

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“…OV infection induced DNA damage, such as the formation of 8-nitroguanine and 8-oxodG, in bile duct epithelial cells in consistent with our previous reports. [15][16][17] The formation of 8-nitroguanine was clearly observed mainly in the nucleus of bile duct epithelium with RNase treatment, suggesting that 8-nitroguanine is formed in genomic DNA. The formation of 8-nitroguanine and 8-oxodG was almost completely inhibited by drug treatment.…”

Section: Discussionmentioning

confidence: 98%

“…O. viverrini infection mediates iNOSdependent DNA damage in intrahepatic bile duct epithelium and inflammatory cells of hamsters, which may play an important role in CCA development. [15][16][17] Therefore, such DNA damage may participate in inflammation-mediated carcinogenesis.Recently, we have reported that OV antigen induces expression of Toll-like receptor 2 (TLR2), leading to nuclear factor-jB (NFjB)-mediated iNOS expression in macrophage cell line.18 TLRs activate homologous signal transduction pathways, leading to nuclear localization of NF-jB/Rel-type transcription factors.19 NFjB is a key player in inflammation that regulates expression of various genes involved in controlling inflammatory response such as proinflammatory mediator and inducible nitric oxide synthase (iNOS) expression. 20,21 Relevantly, NF-jB functions as a tumor promoter in inflammation-associated cancer.…”

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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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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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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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“…The studies on 8-nitroguanine formation in relation to inflammation-related carcinogenesis are summarized in Table 3. We found that 8-nitroguanine was formed in epithelial cells of intrahepatic bile duct using an animal model infected with the liver fluke Opisthorchis viverrini, endemic in northeastern Thailand (Pinlaor et al, 2004a;Pinlaor et al, 2004b;Pinlaor et al, 2003). Administration of the antiparasitic drug praziquantel and the antioxidant curcumin significantly reduced oxidative and nitrative DNA damage Prakobwong et al, 2011).…”

Section: -Nitroguanine Formation In Inflammation-related Carcinogenesismentioning

confidence: 98%

Role of Chronic Inflammation and Resulting DNA Damage in Cervical Carcinogenesis Induced by Human Papillomavirus

Hiraku¹

2012

Human Papillomavirus and Related Diseases - From Bench to Bedside - Research Aspects

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“…8-Nitroguanine was formed in the bile duct epithelium of the liver of hamsters infected with the liver fluke, Opisthorchis viverrini, which causes cancer of intrahepatic bile duct (Pinlaor et al, 2003;Pinlaor et al, 2004a). The treatment with praziquantel, an antiparasitic drug, reduced 8-nitroguanine formation .…”

Section: Application Of Immunochemistry Employing Anti-8-nitroguaninementioning

confidence: 99%

8-Nitroguanine, a Potential Biomarker to Evaluate the Risk of Inflammation-Related Carcinogenesis

Ma¹,

Murata²,

Ohnishi³

et al. 2012

Biomarker

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8-Nitroguanine formation in the liver of hamsters infected with Opisthorchis viverrini

Cited by 103 publications

References 30 publications

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

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

Role of Chronic Inflammation and Resulting DNA Damage in Cervical Carcinogenesis Induced by Human Papillomavirus

8-Nitroguanine, a Potential Biomarker to Evaluate the Risk of Inflammation-Related Carcinogenesis

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