Acetaminophen Overdose Enhances Early Cholangiocarcinoma in Opisthorchiasis Hamsters.

Pranee Sriraj,Atchara Artchayasawat,Ratchadawan Aukkanimart,Panaratana Ratanasuwan,Thidarut Boonmars,Glenn N Borlace,Benjamabhorn Pumhirunroj

doi:10.31557/apjcp.2021.22.12.3903

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.

Highlights

Opisthorchiasis, which is caused by Opisthorchis viverrini infection, is a major public health problem in many Southeast Asian countries, in particular in the northeastern region of Thailand (Sithithaworn and Haswell-Elkins, 2003; Conlan et al, 2011; IARC, 2011)
Acetaminophen is safe at therapeutic doses (1–4 g/day), hepatotoxicity can occur with misuse and overdose
Inflammatory aggregates were found in hepatic tissue of the non-infected acetaminophen control (N-Ac) group, while the O. viverrini infected (OV) and O. viverrini infected acetaminophen (OV-Ac) groups showed inflammatory aggregates surrounding the hepatic bile duct and in the hilar region as well as in hepatic tissue

Summary

Introduction

Opisthorchiasis, which is caused by Opisthorchis viverrini infection, is a major public health problem in many Southeast Asian countries, in particular in the northeastern region of Thailand (Sithithaworn and Haswell-Elkins, 2003; Conlan et al, 2011; IARC, 2011). Opisthorchiasis induced hepatobiliary disease is associated with chronic inflammation, (Bility and Sripa, 2014; Sergei et al, 2010) and is an important determinant for the development of cholangiocarcinoma (CCA), or bile duct cancer (IARC, 2011). Acetaminophen is a major cause of acute liver failure in adults in the United States and many other countries worldwide (Clark, 2001; Brok et al, 2002; Ostapowicz et al, 2002; Lee, 2004; Sumioka et al, 2004; Cooper et al, 2009; Nam et al, 2009; Agarwal et al, 2011) and acute acetaminophen overdose has been shown to lead to hepatic and renal necrosis in humans and experimental animals

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