TY - JOUR

T1 - Prolonged liver fluke infection combined with alcoholization: An experimental mouse model

AU - Avgustinovich, Damira

AU - Kizimenko, Alena

AU - Marenina, Mariya

AU - Lvova, Maria

AU - Kovner, Anna

AU - Orlovskaya, Irina

AU - Toporkova, Ludmila

AU - Goiman, Elena

AU - Tsyganov, Mikhail

AU - Ponomarev, Denis

N1 - Funding Information: The work was supported by the Russian Foundation for Basic Research (grant No. 20-04-00139); a publicly funded project for the Institute of Cytology and Genetics SB RAS (grant No. FWNR-2022-0021); and in part by a state assignment for the Institute of Solid State Chemistry and Mechanochemistry SB RAS (project No. 0301-2021-0005). The authors are grateful to the Multiaccess Facility for Microscopic Analysis of Biological Objects (http://www.bionet.nsc.ru/microscopy/) for the equipment as well as to the Center for Genetic Resources of Laboratory Animals (both at the Institute of Cytology and Genetics SB RAS), which is supported by the Russian Ministry of Science and Higher Education (unique identifier of the project: RFMEFI62119X0023). We are thankful to Nikolai Shevchuk ( http://shevchuk-editing.com/ ) for translating and editing this manuscript (language certificate of September 19, 2022). Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/11

Y1 - 2022/11

N2 - Liver fluke infections disrupt the bile-excreting function of the human liver. Worldwide, excessive alcohol consumption also leads primarily to liver diseases. Our aim was to comprehensively assess the liver state in mice in parallel with the characterization of inflammation when the two adverse factors were combined. C57BL/6 mice were used for the experimental modeling; half of them beforehand were gradually accustomed to consumption of increasing doses of ethanol (from 5% to 20%). Then, half of the animals in each subgroup was infected with Opisthorchis felineus helminths. Finally, the infected (OF), 20% ethanol-consuming (Eth), and subjected to both factors (Eth + OF) mice were compared with no-treatment control. In OF and especially Eth + OF mice, relative liver weight was greater, activities of alanine aminotransferase and aspartate aminotransferase were higher, and bile ducts were considerably enlarged. Eth + OF mice contained noticeably more helminths in the liver than OF mice did. Massive cholangiofibrosis and periductal fibrosis were noted in the liver of the infected mice, especially Eth + OF ones. The liver fluke infection caused inflammatory infiltration and bile duct proliferation. Splenomegaly due to structural changes in the spleen as well as increased levels of interleukin 6 and leukocyte and monocyte counts in the blood reflected substantial inflammation in Eth + OF mice. Thus, in the proposed experimental model, it is shown that a double hit to the liver, i.e., the combination of O. felineus infection with prolonged alcoholization, can be detrimental to both the liver and whole body.

AB - Liver fluke infections disrupt the bile-excreting function of the human liver. Worldwide, excessive alcohol consumption also leads primarily to liver diseases. Our aim was to comprehensively assess the liver state in mice in parallel with the characterization of inflammation when the two adverse factors were combined. C57BL/6 mice were used for the experimental modeling; half of them beforehand were gradually accustomed to consumption of increasing doses of ethanol (from 5% to 20%). Then, half of the animals in each subgroup was infected with Opisthorchis felineus helminths. Finally, the infected (OF), 20% ethanol-consuming (Eth), and subjected to both factors (Eth + OF) mice were compared with no-treatment control. In OF and especially Eth + OF mice, relative liver weight was greater, activities of alanine aminotransferase and aspartate aminotransferase were higher, and bile ducts were considerably enlarged. Eth + OF mice contained noticeably more helminths in the liver than OF mice did. Massive cholangiofibrosis and periductal fibrosis were noted in the liver of the infected mice, especially Eth + OF ones. The liver fluke infection caused inflammatory infiltration and bile duct proliferation. Splenomegaly due to structural changes in the spleen as well as increased levels of interleukin 6 and leukocyte and monocyte counts in the blood reflected substantial inflammation in Eth + OF mice. Thus, in the proposed experimental model, it is shown that a double hit to the liver, i.e., the combination of O. felineus infection with prolonged alcoholization, can be detrimental to both the liver and whole body.

KW - Blood

KW - C57BL/6 mice

KW - Chronic ethanol

KW - Liver

KW - Opisthorchis felineus

KW - Spleen

KW - Aspartate Aminotransferases

KW - Alanine Transaminase

KW - Ethanol

KW - Humans

KW - Mice, Inbred C57BL

KW - Inflammation

KW - Interleukin-6

KW - Animals

KW - Mice

KW - Opisthorchiasis/complications

KW - Opisthorchis

KW - Disease Models, Animal

KW - Alcohol Drinking/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85140658788&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/bd27a348-1553-39e2-abea-5816ae7847b2/

U2 - 10.1016/j.exppara.2022.108399

DO - 10.1016/j.exppara.2022.108399

M3 - Article

C2 - 36228703

AN - SCOPUS:85140658788

VL - 242

JO - Experimental Parasitology

JF - Experimental Parasitology

SN - 0014-4894

M1 - 108399

ER -