title: Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection.
abstract: 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-α, ILβ-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.
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Sejung
authors.initials: S
authors.lastname: Maeng
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Qudsia
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department of Medical Environmental Biology and Research Center for Biomolecules and Biosystems, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Tae Im
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Department of Medical Environmental Biology and Research Center for Biomolecules and Biosystems, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Sung-Jong
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Department of Pathology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeonsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeonsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
authors.affiliation: Department of Parasitology, Inha University School of Medicine, Incheon 400-103, Republic of Korea.
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea. Electronic address: jhpak@amc.seoul.kr.
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
mesh_terms: D000818:Animals; D003003:Clonorchiasis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D003004:Clonorchis sinensis / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Cholangiocarcinoma; Clonorchis sinensis; Excretory-secretory products; Lipid peroxidation; Oxidative stress; Proinflammatory cytokines