title: Inhibitory effect of glutathione on oxidative liver injury induced by dengue virus serotype 2 infections in mice.
abstract: The pathogenesis of dengue virus (DV) infection has not been completely defined and change of redox status mediated by depletion of glutathione (GSH) in host cell is a common result of viral infection. Our previous study has demonstrated that DV serotype 2 (DV2) infection alters host intracellular GSH levels, and exogenous GSH inhibits viral production by modulating the activity of NF-κB in HepG2 cells. GSH is the most powerful intracellular antioxidant and involved in viral infections. Thus, this study was to investigate whether DV2 infection can induce alteration in redox balance and effect of GSH on the disease in HepG2 xenografts SCID mice. Our results revealed that mice infected with DV2 showed alterations in oxidative stress by increasing the level of malondialdehyde (MDA), an end product of lipid peroxidation, and GSSG/GSH ratio. DV2-infected mice also showed a decrease in the activity of catalase (CAT) and total superoxide dismutase (T-SOD) in the serum and/or observed organs, especially the liver. Moreover, DV2 infection resulted in elevated serum levels of the cytokines tumor necrosis factor-α and interlukin-6 and obvious histopathological changes in the liver. The administration of exogenous GSH significantly reversed all of the aforementioned pathological changes and prevented significant liver damage. Furthermore, in vitro treatment of HepG2 cells with antioxidants such as GSH inhibited viral entry as well as the production of reactive oxygen species in HepG2 cells. These results suggest that GSH prevents DV2-induced oxidative stress and liver injury in mice by inhibiting proinflammatory cytokine production, and GSH and may be a promising therapeutic agent for prevention of oxidative liver damage during DV infection.
authors: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors: Juan
authors: J
authors: Wang
authors: Yanlei
authors: Y
authors: Chen
authors: Na
authors: N
authors: Gao
authors: Yisong
authors: Y
authors: Wang
authors: Yanping
authors: Y
authors: Tian
authors: Jiangman
authors: J
authors: Wu
authors: Junlei
authors: J
authors: Zhang
authors: Junping
authors: J
authors: Zhu
authors: Dongying
authors: D
authors: Fan
authors: Jing
authors: J
authors: An
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000097:blood; D003124:Colorimetry; D003715:Dengue / Q000188:drug therapy* / Q000473:pathology*; D003716:Dengue Virus / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006652:Histological Techniques; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
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