Abstract
Opisthorchis viverrini infection is one of the risk factors for cholangiocarcinoma (CCA) in northeast Thailand, a region with one of the highest reported incidence rates of CCA. The traditional practice of eating raw fish, repeated exposure to liver flukes, and consumption of nitrosamine-contaminated food are major risk factors for CCA. So far, there have been no reports about which northeastern traditional dishes may be involved in CCA development. The present study, thus, investigated the effects of traditional foods. It focused specifically on the consumption of fermented foods in combination with O. viverrini infection in hamsters. Syrian hamsters were divided into six groups: (i) normal hamsters, (ii) O. viverrini infection only and (iii)–(vi) O. viverrini infection plus fermented foods (pla som—fish fermented for 1 day), som wua—fermented beef, som phag—fermented vegetables, and pla ra—fish fermented for 6 months. Syrian hamster livers were used for analysis of histopathological changes through hematoxylin and eosin; Sirius Red; and immunohistostaining for cytokeratin-19, proliferating cell nuclear antigen, and CA19-9. Hamster sera were used for liver and kidney function tests. Results of all O. viverrini-infected groups and fermented food groups showed that histopathological changes consisted primarily of aggregations of inflammatory cells surrounding the hepatic bile duct, especially at the hilar region. However, there was a difference in virulence. Interestingly, aggregations of inflammatory cells, new bile duct formation, and fibrosis were observed in subcapsular hepatic tissue, which correlated to positive immunohistochemical staining and increased liver function test. The present study suggests that fermented food consumption can exacerbate cholangitis and cholangiofibrosis, which are risk factors for cholangiocarcinoma-associated opisthorchiasis.
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Abbreviations
- CCA:
-
Cholangiocarcinoma
- PS:
-
Pla som
- SP:
-
Som phug
- PR:
-
Pla ra
- SW:
-
Som wua
- CK-19:
-
Cytokeratin 19
- PCNA:
-
Proliferating cell nuclear antigen
- CA19-9:
-
Carbohydrate antigen19-9
References
Bansal AK, Bansal M, Soni G, Bhatnagar D (2005) Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes. Hum Exp Toxicol 24:297–302
Bhamarapravati N, Thamavit W (1978) Animal studies on liver fluke infestation, dimethylnitrosamine, and bile duct carcinoma. Lancet 1:206–207
Boonjaraspinyo S, Boonmars T, Aromdee C, Kaewsamut B (2010) Effect of fingerroot on reducing inflammatory cells in hamster infected with Opisthorchis viverrini and N-nitrosodimethylamine administration. Parasitol Res 106:1485–1489
Boonmars T, Srisawangwong T, Srirach P, Kaewsamut B, Pinlaor S, Sithithaworn P (2007) Apoptosis-related gene expressions in hamsters re-infected with Opisthorchis viverrini and re-treated with praziquantel. Parasitol Res 102:57–62
Boonmars T, Srirach P, Kaewsamut B, Srisawangwong T, Pinlaor S, Pinlaor P, Yongvanit P, Sithithaworn P (2008) Apoptosis-related gene expression in hamster opisthorchiasis post-praziquantel treatment. Parasitol Res 102:447–455
Boonmars T, Wu Z, Boonjaruspinyo S, Puapairoj A, Kaewsamut B, Nagano I, Pinlaor S, Yongvanit P, Wonkchalee O, Juasook A, Sudsarn P, Srisawangwong T (2011) Involvement of c-Ski oncoprotein in carcinogenesis of cholangiocacinoma induced by Opisthorchis viverrini and N-nitrosodimethylamine. Pathol Oncol Res 17:219–227
Burchill SA, Bradbury MF, Pittman K, Southgate J, Smith B, Selby P (1995) Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction. Br J Cancer 71:278–281
Conlan JV, Sripa B, Attwood S, Newton PN (2011) A review of parasitic zoonoses in a changing Southeast Asia. Vet Parasitol 182:22–40
Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD (2013) Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology 145:521–536
Flavell DJ, Lucas SB (1983) Promotion of N-nitrosodimethylamine-initiated bile duct carcinogenesis in the hamster by the human liver fluke, Opisthorchis viverrini. Carcinogenesis 4:927–930
Fong YY, Chan WC (1977) Nitrate, nitrite, dimethylnitrosamine and N-nitrosopyrrolidine in some Chinese food products. Food Cosmet Toxicol 15:143–145
Hashimoto T, Ibi M, Matsuno K, Nakashima S, Tanigawa T, Yoshikawa T, Yabe-Nishimura C (2004) An endogenous metabolite of dopamine, 3,4-dihydroxyphenylethanol, acts as a unique cytoprotective agent against oxidative stress-induced injury. Free Radic Biol Med 36:555–564
Haswell-Elkins MR, Satarug S, Tsuda M, Mairiang E, Esumi H, Sithithaworn P, Mairiang P, Saitoh M, Yongvanit P, Elkins DB (1994) Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis. Mutat Res 305:241–252
Herrold KM (1967) Histogenesis of malignant liver tumors induced by dimethylnitrosamine. An experimental study in Syrian hamsters. J Natl Cancer Inst 39:1099–1111
Honjo S, Srivatanakul P, Sriplung H, Kikukawa H, Hanai S, Uchida K, Todoroki T, Jedpiyawongse A, Kittiwatanachot P, Sripa B, Deerasamee S, Miwa M (2005) Genetic and environmental determinants of risk for cholangiocarcinoma via Opisthorchis viverrini in a densely infested area in Nakhon Phanom, northeast Thailand. Int J Cancer 117:854–860
Hotchkiss JH (1989) Preformed N-nitroso compounds in foods and beverages. Cancer Surv 8:295–321
Huang PH, Stewart BW (1978) Dimethylnitrosamine-induced structural damage to DNA results from repair of 6-methylguanine rather than repair of 7-methylguanine. Cancer Lett 5:161–166
IARC (2011) Opisthorchis viverrini and Clonorchis sinensis. IARC Monogr Eval Carcinog Risks Hum 100:347–376
Juasook A, Boonmars T, Kaewkes S, Loilome W, Veteewuthacharn K, Wu Z, Yongvanit P (2012) Anti-inflammatory effect of prednisolone on the growth of human liver fluke in experimental opisthorchiasis. Parasitol Res 110:2271–2279
Juasook A, Aukkanimart R, Boonmars T, Sudsarn P, Wonkchalee N, Laummaunwai P, Sriraj P (2013a) Tumor-related gene changes in immunosuppressive Syrian hamster cholangiocarcinoma. Pathol Oncol Res 19:785–794
Juasook A, Boonmars T, Wu Z, Loilome W, Veteewuthacharn K, Namwat N, Sudsarn P, Wonkchalee O, Sriraj P, Aukkanimart R (2013b) Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine. Pathol Oncol Res 19:55–62
Lee M, Lee Y, Soltermann F, von Gunten U (2013) Analysis of N-nitrosamines and other nitro(so) compounds in water by high-performance liquid chromatography with post-column UV photolysis/Griess reaction. Water Res 47:4893–4903
Mao Q, Xie Z, Wang X, Chen W, Ren M, Shang M, Lei H, Tian Y, Li S, Liang P, Chen T, Liang C, Xu J, Li X, Huang Y, Yu X (2015) Clonorchis sinensis ferritin heavy chain triggers free radicals and mediates inflammation signaling in human hepatic stellate cells. Parasitol Res 114:659–670
Migasena P (1982) Role of village volunteers in a food and nutrition monitoring system. J Med Assoc Thail 65:399–401
Pinlaor S, Hiraku Y, Ma N, Yongvanit P, Semba R, Oikawa S, Murata M, Sripa B, Sithithaworn P, Kawanishi S (2004) Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis. Nitric Oxide 11:175–183
Satarug S, Lang MA, Yongvanit P, Sithithaworn P, Mairiang E, Mairiang P, Pelkonen P, Bartsch H, Haswell-Elkins MR (1996) Induction of cytochrome P450 2A6 expression in humans by the carcinogenic parasite infection, Opisthorchiasis viverrini. Cancer Epidemiol Biomarkers Prev 5:795–800
Seel DJ, Kawabata T, Nakamura M, Ishibashi T, Hamano M, Mashimo M, Shin SH, Sakamoto K, Jhee EC, Watanabe S (1994) N-nitroso compounds in two nitrosated food products in southwest Korea. Food Chem Toxicol 32:1117–1123
Sithithaworn P, Haswell-Elkins M (2003) Epidemiology of Opisthorchis viverrini. Acta Trop 88:187–194
Srianujata S, Tangbanleukal L, Bunyaratvej S, Valyasevi A (1984) Nitrate and nitrite in saliva and urine of inhabitants of areas of low and high incidence of cholangiocarcinoma in Thailand. IARC Sci Publ: 921–927
Sripa B, Kaewkes S (2002) Gall bladder and extrahepatic bile duct changes in Opisthorchis viverrini-infected hamsters. Acta Trop 83:29–36
Sripa B, Thinkhamrop B, Mairiang E, Laha T, Kaewkes S, Sithithaworn P, Periago MV, Bhudhisawasdi V, Yonglitthipagon P, Mulvenna J, Brindley PJ, Loukas A, Bethony JM (2012) Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini. PLoS Negl Trop Dis 6, e1654
Sriraj P, Aukkanimart R, Boonmars T, Juasook A, Sudsarn P, Wonkchalee N, Pairojkul C, Waraasawapati S, Laummaunwai P, Boonjaraspinyo S (2013) Does a combination of opisthorchiasis and ethyl alcohol consumption enhance early cholangiofibrosis, the risk of cholangiocarcinoma? Parasitol Res 112:2971–2981
Srivatanakul P, Ohshima H, Khlat M, Parkin M, Sukaryodhin S, Brouet I, Bartsch H (1991a) Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer 48:821–825
Srivatanakul P, Parkin DM, Jiang YZ, Khlat M, Kao-Ian UT, Sontipong S, Wild C (1991b) The role of infection by Opisthorchis viverrini, hepatitis B virus, and aflatoxin exposure in the etiology of liver cancer in Thailand. A correlation study. Cancer 68:2411–2417
Sudsarn P, Boonmars T, Ruangjirachuporn W, Namwat N, Loilome W, Sriraj P, Aukkanimart R, Nadchanan W, Jiraporn S (2016) Combination of praziquantel and aspirin minimizes liver pathology of hamster Opisthorchis viverrini Infection associated cholangiocarcinoma. Pathol Oncol Res 22:57–65
Tannenbaum SR (1985) Diet and exposure to N-nitroso compounds. Princess Takamatsu Symp 16:67–75
Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S (1978) Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res 38:4634–4639
Van Bergen P, Rauhala P, Spooner CM, Chiueh CC (1999) Hemoglobin and iron-evoked oxidative stress in the brain: protection by bile pigments, manganese and S-nitrosoglutathione. Free Radic Res 31:631–640
Wogan GN, Tannenbaum SR (1975) Environmental N-nitroso compounds: implications for public health. Toxicol Appl Pharmacol 31:375–383
Wonkchalee O, Boonmars T, Kaewkes S, Chamgramol Y, Aromdee C, Wu Z, Juasook A, Sudsarn P, Boonjaraspinyo S, Pairojkul C (2012) Comparative studies on animal models for Opisthorchis viverrini infection: host interaction through susceptibility and pathology. Parasitol Res 110:1213–1223
Wu W, Feng A, Huang Y (2015) Research and control of advanced schistosomiasis japonica in China. Parasitol Res 114:17–27
Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214:199–210
Zhou L, Shang M, Shi M, Zhao L, Lin Z, Chen T, Wu Y, Tang Z, Sun H, Yu J, Huang Y, Yu X (2016) Clonorchis sinensis lysophospholipase inhibits TGF-β1-induced expression of pro-fibrogenic genes through attenuating the activations of Smad3, JNK2, and ERK1/2 in hepatic stellate cell line LX-2. Parasitol Res 115:643–650
Acknowledgments
This study was supported by grants from the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHep-GMS), Research Grant for New Scholar (grant no. MRG5980097), and TRF Senior Research Scholar (grant no. RTA5880001). English was improved by Dr. Christopher Salisbury and Dr. Dylan Southard.
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All protocols, including housing and animal laboratory management, were approved by the Animal Ethics Committee at Khon Kaen University (AEKKU 47/2556).
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Sriraj, P., Boonmars, T., Aukkanimart, R. et al. A combination of liver fluke infection and traditional northeastern Thai foods associated with cholangiocarcinoma development. Parasitol Res 115, 3843–3852 (2016). https://doi.org/10.1007/s00436-016-5148-5
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DOI: https://doi.org/10.1007/s00436-016-5148-5