Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection

다국어 초록 (Multilingual Abstract)

<P>Clonorchis sinensis is a high-risk pathogenic helminth that strongly provokes inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma in chronically infected individuals. Chronic inflammation is associated with an increased risk of various cancers due to the disruption of redox homeostasis. Accordingly, the present study was conducted to examine the time course relationship between histopathological changes and the appearance of oxidative stress markers, including lipid peroxidation, enzymes involved in lipid peroxidation, and mutagenic DNA adducts in the livers of mice infected with C. sinensis, as well as proinflammatory cytokines in infected mouse sera. Histopathological phenotypes such as bile duct epithelial hyperplasia, periductal fibrosis, edema and inflammatory infiltration increased in infected livers in a time-dependent manner. Intense immunoreactivity of lipid peroxidation products (4-hydroxy-2-nonenal; malondialdehyde), cyclooxygenase-2, 5-lipoxygenase and 8-oxo-7,8-dihydro-2'-deoxyguanosine were concomitantly observed in these injured regions. We also found elevated expressions of cyclooxygenase-2 and 5-lipoxygenase in C sinensis excretory-secretory product-treated cholangiocarcinoma cells. Moreover, the levels of proinflammatory cytokines such as TNF-alpha, IL beta-1 and IL-6 were differentially upregulated in infected sera. With regard to oxidative stress-mediated carcinogenesis, our findings suggest that C sinensis infestation may disrupt host redox homeostasis, creating a damaging environment that favors the development of advanced hepatobiliary diseases such as clonorchiasis-associated cholangiocarcinoma. (C) 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.</P>