Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma

Pakkayanee Sudsarn; Thidarut Boonmars; Wipaporn Ruangjirachuporn; Nisana Namwat; Watcharin Loilome; Pranee Sriraj; Ratchadawan Aukkanimart; Wonkchalee Nadchanan; Songsri Jiraporn

doi:10.1007/s12253-015-9967-y

Pathology & Oncology Research

January 2016, Volume 22, Issue 1, pp 57–65

Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma

Authors
Authors and affiliations

Pakkayanee Sudsarn
Thidarut BoonmarsEmail author
Wipaporn Ruangjirachuporn
Nisana Namwat
Watcharin Loilome
Pranee Sriraj
Ratchadawan Aukkanimart
Wonkchalee Nadchanan
Songsri Jiraporn

Original Article

First Online:: 16 August 2015

Received:: 11 September 2014
Accepted:: 04 August 2015

DOI: 10.1007/s12253-015-9967-y

Cite this article as:: Sudsarn, P., Boonmars, T., Ruangjirachuporn, W. et al. Pathol. Oncol. Res. (2016) 22: 57. doi:10.1007/s12253-015-9967-y

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Abstract

Opisthorchiasis is one of the major risk factors for cholangiocarcinoma (CCA) in northeastern Thailand. An effective drug for killing this parasite is praziquantel. Recently, several reports have shown that with frequent use, praziquantel may itself be a CCA risk and can cause liver cell damage from an immunopathological response after parasite death. Aspirin has many properties including anti-inflammation and anti-cancer. Therefore, we use of aspirin (As) and praziquantel (Pz) to improve hepatobiliary system function in hamsters infected with Opisthorchis viverrini (OV) and or administered N-nitrosodimethylamine (ND). Livers of OVNDAsPz, appeared healthy macroscopically, suggesting slow progression of cholangiocarcinoma evident by extent of fibrosis and bile duct cell proliferation was less than OVND although aggregations of inflammatory cells remained. Proliferating cell nuclear antigen (PCNA), cytokeratin 19 (CK19), and cancer antigen (CA19-9) staining were strongly positive in OVND, but were only slight in OVNDAs. Moreover, OVNDAsPz, appeared a few inflammatory infiltrations, bile duct proliferation, fibrosis and CCA area than the OVNDAs group. Thirty seven point five percent of hamster in this group could not develop CCA. These findings suggest that using aspirin combination with praziquantel treatment can improve the hepatobiliary system after O. viverrini infection and reduce the risk of CCA.

Keywords

Praziquantel Aspirin Opisthorchis viverrini N-nitrosodimethylamine Cholangiocarcinoma Syrian hamster

References

1.
IARC (2011) A review of human carcinogens part B: biological agents (Opisthorchis viverrini and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 100:347–3762Google Scholar
2.
Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, Pairojkul C, Bhudhisawasdi V, Tesana S, Thinkamrop B, Bethony JM, Loukas A, Brindley PJ (2007) Liver fluke induces cholangiocarcinoma. PLoS Med 4(7):e201
3.
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(3):447–455CrossRefPubMedGoogle Scholar
4.
Pinlaor S, Prakobwong S, Hiraku Y, Kaewsamut B, Dechakhamphu S, Boonmars T, Sithithaworn P, Pinlaor P, Ma N, Yongvanit P, Kawanishi S (2008) Oxidative and nitrative stress in Opisthorchis viverrini-infected hamsters: an indirect effect after praziquantel treatment. AmJTrop Med Hyg 78(4):564–573Google Scholar
5.
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(6):1485–1489CrossRefPubMedGoogle Scholar
6.
Jongthawin J, Techasen A, Loilome W, Yongvanit P, Namwat N (2012) Anti-inflammatory agents suppress the prostaglandin E2 production and migration ability of cholangiocarcinoma cell lines. Asian Pac J Cancer Prev 13(Suppl):47–51PubMedGoogle Scholar
7.
Plengsuriyakarn T, Viyanant V, Eursitthichai V, Picha P, Kupradinun P, Itharat A, Na-Bangchang K (2012) Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models. BMC Complement Altern Med 12:23PubMedCentralCrossRefPubMedGoogle Scholar
8.
Boonjaraspinyo S, Boonmars T, Aromdee C, Srisawangwong T, Kaewsamut B, Pinlaor S, Yongvanit P, Puapairoj A (2009) Turmeric reduces inflammatory cells in hamster opisthorchiasis. Parasitol Res 105(5):1459–1463CrossRefPubMedGoogle Scholar
9.
Pinlaor S, Prakobwong S, Hiraku Y, Pinlaor P, Laothong U, Yongvanit P (2010) Reduction of periductal fibrosis in liver fluke-infected hamsters after long-term curcumin treatment. Eur J Pharmacol 638(1–3):134–141CrossRefPubMedGoogle Scholar
10.
Prakobwong S, Khoontawad J, Yongvanit P, Pairojkul C, Hiraku Y, Sithithaworn P, Pinlaor P, Aggarwal BB, Pinlaor S (2011) Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing inflammation-mediated molecular events related to multistep carcinogenesis. Int J Cancer 129(1):88–100CrossRefPubMedGoogle Scholar
11.
Wonkchalee O, Boonmars T, Aromdee C, Laummaunwai P, Khunkitti W, Vaeteewoottacharn K, Sriraj P, Aukkanimart R, Loilome W, Chamgramol Y, Pairojkul C, Wu Z, Juasook A, Sudsarn P (2012) Anti-inflammatory, antioxidant and hepatoprotective effects of Thunbergia laurifolia Linn. On experimental opisthorchiasis. Parasitol Res 111(1):353–359CrossRefPubMedGoogle Scholar
12.
Gu Q, Wang JD, Xia HH, Lin MC, He H, Zou B, Tu SP, Yang Y, Liu XG, Lam SK, Wong WM, Chan AO, Yuen MF, Kung HF, Wong BC (2005) Activation of the caspase-8/bid and Bax pathways in aspirin-induced apoptosis in gastric cancer. Carcinogenesis 26(3):541–546CrossRefPubMedGoogle Scholar
13.
Redlak MJ, Power JJ, Miller TA (2005) Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol 289(4):G731–G738PubMedGoogle Scholar
14.
Zimmermann KC, Waterhouse NJ, Goldstein JC, Schuler M, Green DR (2000) Aspirin induces apoptosis through release of cytochrome c from mitochondria. Neoplasia 2(6):505–513PubMedCentralCrossRefPubMedGoogle Scholar
15.
Bousserouel S, Gosse F, Bouhadjar M, Soler L, Marescaux J, Raul F (2010) Long-term administration of aspirin inhibits tumour formation and triggers anti-neoplastic molecular changes in a pre-clinical model of colon carcinogenesis. Oncol Rep 23(2):511–517PubMedGoogle Scholar
16.
Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, Hind D, Tappenden P (2010) Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol Assess 14(32):1–206CrossRefGoogle Scholar
17.
Larkins TL, Nowell M, Singh S, Sanford GL (2006) Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer 6:181PubMedCentralCrossRefPubMedGoogle Scholar
18.
Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW, Jr. (1993) Aspirin use and risk of fatal cancer. Cancer Res 53(6):1322–1327PubMedGoogle Scholar
19.
Boonjaraspinyo S, Boonmars T, Aromdee C, Puapairoj A, Wu Z (2011) Indirect effect of a turmeric diet: enhanced bile duct proliferation in Syrian hamsters with a combination of partial obstruction by Opisthorchis viverrini infection and inflammation by N-nitrosodimethylamine administration. Parasitol Res 108(1):7–14CrossRefPubMedGoogle Scholar
20.
Juasook A, Boonmars T, Wu Z, Loilome W, Veteewuthacharn K, Namwat N, Sudsarn P, Wonkchalee O, Sriraj P, Aukkanimart R (2013) Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine. Pathol Oncol Res 19(1):55–62CrossRefPubMedGoogle Scholar
21.
Thamavit W, Pairojkul C, Tiwawech D, Shirai T, Ito N (1994) Strong promoting effect of Opisthorchis viverrini infection on dimethylnitrosamine-initiated hamster liver. Cancer Lett 78(1–3):121–125CrossRefPubMedGoogle Scholar
22.
Miliaras S, Miliaras D, Vrettou E, Zavitsanakis A, Kiskinis D (2004) The effect of aspirin and high fibre diet on colorectal carcinoma: a comparative experimental study. Tech Coloproctol 8(Suppl 1):s59–s61CrossRefPubMedGoogle Scholar
23.
Wonkchalee O, Boonmars T, Kaewkes S, Chamgramol Y, Pairojkul C, Wu Z, Juasook A, Sudsarn P, Boonjaraspinyo S (2011) Opisthorchis viverrini infection causes liver and biliary cirrhosis in gerbils. Parasitol Res 109(3):545–551CrossRefPubMedGoogle Scholar
24.
Muerkoster S, Wegehenkel K, Arlt A, Witt M, Sipos B, Kruse ML, Sebens T, Kloppel G, Kalthoff H, Folsch UR, Schafer H (2004) Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta. Cancer Res 64(4):1331–1337CrossRefPubMedGoogle Scholar
25.
IARC (1994) Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61:121–175Google Scholar
26.
Haswell-Elkins MR, Mairiang E, Mairiang P, Chaiyakum J, Chamadol N, Loapaiboon V, Sithithaworn P, Elkins DB (1994) Cross-sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand. Int J Cancer 59(4):505–509CrossRefPubMedGoogle Scholar
27.
Sripa B, Pairojkul C (2008) Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol 24(3):349–356PubMedCentralCrossRefPubMedGoogle Scholar
28.
Srivatanakul P (2001) Epidemiology of liver cancer in Thailand. Asian Pac J Cancer Prev 2(2):117–121
29.
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(5):854–860CrossRefPubMedGoogle Scholar
30.
Songserm N, Promthet S, Sithithaworn P, Pientong C, Ekalaksananan T, Chopjitt P, Parkin DM (2012) Risk factors for cholangiocarcinoma in high-risk area of Thailand: role of lifestyle, diet and methylenetetrahydrofolate reductase polymorphisms. Cancer Epidemiol 36(2):e89–e94CrossRefPubMedGoogle Scholar
31.
Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin DM (2004) Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, northeast Thailand. Tropical Med Int Health 9(5):588–594CrossRefGoogle Scholar
32.
Harris RE, Namboodiri KK, Farrar WB (1996) Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 7(2):203–205CrossRefPubMedGoogle Scholar
33.
Bardia A, Olson JE, Vachon CM, Lazovich D, Vierkant RA, Wang AH, Limburg PJ, Anderson KE, Cerhan JR (2011) Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study. Breast Cancer Res Treat 126(1):149–155PubMedCentralCrossRefPubMedGoogle Scholar
34.
Bhattacharyya M, Girish GV, Ghosh R, Chakraborty S, Sinha AK (2010) Acetyl salicylic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients [corrected]. Cancer Sci 101(10):2105–2109CrossRefPubMedGoogle Scholar
35.
Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28(9):1467–1472PubMedCentralCrossRefPubMedGoogle Scholar
36.
Benamouzig R, Uzzan B, Deyra J, Martin A, Girard B, Little J, Chaussade S (2012) Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial. Gut 61(2):255–261CrossRefPubMedGoogle Scholar
37.
Chan AT, Ogino S, Fuchs CS (2009) Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302(6):649–658PubMedCentralCrossRefPubMedGoogle Scholar
38.
Din FV, Theodoratou E, Farrington SM, Tenesa A, Barnetson RA, Cetnarskyj R, Stark L, Porteous ME, Campbell H, Dunlop MG (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59(12):1670–1679CrossRefPubMedGoogle Scholar
39.
Fendrich V, Chen NM, Neef M, Waldmann J, Buchholz M, Feldmann G, Slater EP, Maitra A, Bartsch DK (2010) The angiotensin-I-converting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Gut 59(5):630–637CrossRefPubMedGoogle Scholar
40.
Sclabas GM, Uwagawa T, Schmidt C, Hess KR, Evans DB, Abbruzzese JL, Chiao PJ (2005) Nuclear factor kappa B activation is a potential target for preventing pancreatic carcinoma by aspirin. Cancer 103(12):2485–2490CrossRefPubMedGoogle Scholar
41.
Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19–9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 33(3):266–270CrossRefPubMedGoogle Scholar
42.
Wang Z, Tian YP (2014) Clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma. Mol Clin Oncol 2 (2):265–268
43.
Cai WK, Lin JJ, He GH, Wang H, Lu JH, Yang GS (2014) Preoperative serum CA19-9 levels is an independent prognostic factor in patients with resected hilar cholangiocarcinoma. Int J Clin Exp Pathol 7(11):7890–7898PubMedCentralPubMedGoogle Scholar
44.
Lumachi F, Lo Re G, Tozzoli R, D'Aurizio F, Facomer F, Chiara GB, Basso SM (2014) Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19–9, cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting cholangiocarcinoma: a preliminary case–control study. Anticancer Res 34(11):6663–6667PubMedGoogle Scholar
45.
Juasook A, Aukkanimart R, Boonmars T, Sudsarn P, Wonkchalee N, Laummaunwai P, Sriraj P (2013) Tumor-related gene changes in immunosuppressive Syrian hamster cholangiocarcinoma. Pathol Oncol Res 19(4):785–794CrossRefPubMedGoogle Scholar
46.
Assy N, Hussein O, Khalil A, Luder A, Szvalb S, Paizi M, Spira G (2007) The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis. Dig Dis Sci 52(5):1187–1193CrossRefPubMedGoogle Scholar

Copyright information

Authors and Affiliations

Pakkayanee Sudsarn
- 1
- 2
Thidarut Boonmars
- 1
- 3
Email author
Wipaporn Ruangjirachuporn
- 1
Nisana Namwat
- 3
- 4
Watcharin Loilome
- 3
- 4
Pranee Sriraj
- 3
- 5
Ratchadawan Aukkanimart
- 3
- 5
Wonkchalee Nadchanan
- 3
Songsri Jiraporn
- 1
- 3

1.Department of Parasitology, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
2.Faculty of Agricultural TechnologyBurapha University Sakaeo CampusSakaeoThailand
3.Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen UniversityKhon KaenThailand
4.Department of Biochemistry, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
5.Rajamangala University of Technology Isan Sakonnakhon CampusSakonnakhonThailand

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Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma

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