Journal Article

Opisthorchis felineus infection provokes time-dependent accumulation of oxidative hepatobiliary lesions in the injured hamster liver

Pakharukova, Mariya Y., Kapushchak, Yaroslav K., Mordvinov, Viatcheslav A., Zaparina, Oxana G., Baginskaya, Nina V.

2019

Overview

Opisthorchiasis caused by food-borne trematode Opisthorchis felineus is a substantial public health problem, with 17 million persons infected worldwide. This chronic disease is associated with hepatobiliary inflammation, cholangiocyte dysplasia, cholangiofibrosis, intraepithelial neoplasia, and even cholangiocarcinoma among chronically infected individuals. To provide first insights into the mechanism by which O. felineus infection causes precancerous liver lesions, we investigated the level of oxidative stress (lipid peroxidation byproducts and 8-hydroxy-2'-deoxyguanosine) as well as the time course profiles of chronic inflammation and fibrogenesis markers in the dynamics of opisthorchiasis from 1 month to 1.5 years postinfection in an experimental model based on golden hamsters Mesocricetus auratus. For the first time, we showed that O. felineus infection provokes time-dependent accumulation of oxidative hepatobiliary lesions in the injured liver of hamsters. In particular, over the course of infection, lipid peroxidation byproducts 4-hydroxynonenal and malondialdehyde were upregulated; these changes in general correlate with the dynamics of hepatic histopathological changes. We detected macrophages with various immunophenotypes and elevated levels of CD68, COX2, and CD163 in the O. felineus-infected animals. Meanwhile, there was direct time-dependent elevation of TNF-α (R = 0.79; p < 0.001) and CD163 protein levels (R = 0.58; p = 0.022). We also provide quantitative data about epithelial hyperplasia marker CK7 and a marker of myofibroblast activation (α smooth muscle actin). Our present data provide first insights into the histopathological mechanism by which O. felineus infection causes liver injuries. These findings support the inclusion of O. felineus in Group 1 of biological carcinogens.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 4-Hydroxynonenal / Accumulation / Actin / Animals / Biliary tract cancer / Biology and Life Sciences / Biomarkers / Biomarkers - metabolism / Byproducts / Cancer / Carcinogens / CD163 antigen / Cellular biology / Change detection / Cholangiocarcinoma / Chronic diseases / Chronic illnesses / Cricetinae / Cyclooxygenase-2 / Deoxyguanosine / Deoxyribonucleic acid / Development and progression / Digestive System Diseases - complications / Digestive System Diseases - genetics / Digestive System Diseases - metabolism / Digestive System Diseases - pathology / Disease Models, Animal / DNA / DNA Damage / Dysplasia / Experiments / Fluke infections / Hamsters / Health aspects / Hyperplasia / Infections / Inflammation / Injuries / Laboratories / Lesions / Level (quantity) / Lipid Peroxidation / Lipids / Liver / Liver - metabolism / Liver - pathology / Liver research / Macrophages / Malondialdehyde / Medical research / Medicine and Health Sciences / Metabolites / Muscle proteins / Muscles / Opisthorchiasis - complications / Opisthorchis - physiology / Opisthorchis felineus / Oxidative Stress / Parasites / Pathogens / Peroxidation / Public health / Research and Analysis Methods / Smooth muscle / Time dependence / Time Factors / Tumor necrosis factor-α