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Imbalance in the glutathione system in Opisthorchis felineus infected liver promotes hepatic fibrosis

Author:
Perina, Ekaterina A., Ivanov, Vladimir V., Pershina, Alexandra G., Perekucha, Natalya A., Dzyuman, Anna N., Kaminskii, Ilya P., Saltykova, Irina V., Sazonov, Alexey E., Ogorodova, Ludmila M.
Source:
Acta tropica 2019 v.192 pp. 41-48
ISSN:
0001-706X
Subject:
Opisthorchis, acetylcysteine, animal models, collagen, glutathione, glutathione peroxidase, glutathione transferase, liver, liver cirrhosis, liver flukes, opisthorchiasis, oxidation, oxidative stress
Abstract:
Although data on oxidative stress during liver fluke infection have been previously presented, a comprehensive study of the glutathione system that plays a crucial role in scavenging of reactive oxygen species (ROS) and detoxification of primary and secondary oxidation products has not been addressed yet. In the present study, the hepatic glutathione system was investigated in a hamster model of experimental opisthorchiasis infection. It was shown that chronic oxidative stress in an Opisthorchis felineus infected liver, evidenced by abundant hydroperoxide accumulation, leads to strong imbalance in the hepatic glutathione system, namely the depletion of reduced form of glutathione (GSH), lowering of the GSH/GSSG ratio, and a decrease in the glutathione peroxidase and glyoxalase 1 activity. O. felineus infection provokes hepatocellular damage that results in the progression of liver fibrosis, accompanied by an increase in collagen deposition in the hepatic tissue. Modulation of hepatic GSH levels in the O. felineus infected liver through N-acetylcysteine (NAC) or l-buthionine-S, R-sulfoxinine (BSO) treatments lead to changes in expression and activity of glutathione S-transferase and glyoxalase I as well as markedly decreases or increases collagen content in the O. felineus infected liver and the severity of liver fibrosis, respectively. Thus, the glutathione system can be considered as a target for liver protection from O. felineus-induced injury.
Agid:
6280083