Acetaminophen Overdose Enhances Early Cholangiocarcinoma in Opisthorchiasis Hamsters

Document Type : Research Articles

Authors

1 Department of Traditional Medicine, Faculty of Natural Resources, Rajamangala University of Technology ISAN Sakon Nakhon Campus, Sakon Nakhon 47160, Thailand.

2 Neglected, Zoonosis and Vector Borne Disease Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.

3 Cholangiocarcinoma Research institute, Khon Kaen University,Khon Kaen 40002, Thailand.

4 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

5 Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

6 Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.

7 Program in Animal Science, Faculty of Agricultural Technology, Sakon Nakhon Rajabhat University, Sakon Nakhon, 47000, Thailand.

Abstract

Opisthorchiasis which exerted by infection of Opisthorchis viverrini is strongly related to the incident of cholangiocarcinoma (CCA) in many Southeast Asian countries northeastern of Thailand. The O. viverrini infection is primarily caused by raw fish consumption, and repeated exposure to liver fluke. Meanwhile, acetaminophen is usually medicated to relieve pain in particularly people in northeast Thailand. Objective: This study therefore aimed at investigating effects of acetaminophen on pathogenesis in hamsters for opisthorchiasis. Methods: There were 4 groups of hamsters: i) uninfected hamster (N); ii) sole acetaminophen administration (N-Ac); iii) sole O. viverrini infection (OV); and iv) combination of O. viverrini infection and acetaminophen (OV-Ac) on pathology of hamsters for 1 month post infection. For analysis of histopathological changes through hematoxylin and eosin, Sirius red and immunohistostaining for Cytokeratin 19 (CK-19), Proliferating cell nuclear antigen (PCNA) and CA 19-9, serum’s hamsters were used detected for liver function tests and tumor-related genes expression. Results: After 1 month under these treatments, the OV-Ac showed significantly higher CCA risk, including inflammatory cells were aggregations around bile duct, new bile duct and fibrosis in subcapsular hepatic tissues, than other treatments. These pathological parameters were positively correlated with immunohistochemical staining derived from CK-19, PCNA and CA 19-9. In addition, OV-Ac had significantly higher liver function tests (ALT). Conclusion: Combined intake of liver fluke-contaminated raw fishes and acetaminophen rendered more severity of CCA than sole consumption of the contaminated raw fishes. 

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