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.

Supplementation of Vitamin E Protects Chickens from Newcastle Disease Virus-Mediated Exacerbation of Intestinal Oxidative Stress and Tissue Damage

“…E significantly prevented the oxidative stress induced by NDV challenge. Our results are consistent with several reported studies, in which authors had demonstrated an increase in oxidative stress by infection of different RNA viruses like influenza virus [11,12,43], hepatitis virus [44,45], human immunodeficiency virus [46], and dengue virus [47]. Infection of chickens with mesogenic NDV also showed the comparable results of decreased activities of CAT, GST and increased levels of MDA [17].…”

A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria

“…The ability to shift the redox homeostasis of the host is shared by many other viruses, bacteria and protozoa. As shown in Table 1, many infections caused by intracellular pathogens result in a 2-4-fold decrease in the GSH: GSSG ratio of the host cell221222324252627282930313233. Importantly, this altered redox state is often utilized by the pathogen to facilitate its pathogenesis and/or transmission.…”

Association between proinflammatory cytokines and lipid peroxidation in patients with severe dengue disease around defervescence

“…In the study of Wang et al, significantly elevated levels of TNF-a were observed in DENV type 2 infected mice, whereas reduced TNF-a levels were obtained in the presence of antioxidant. 39 This shows that the presence of antioxidants could inhibit the release of proinflammatory cytokines by inhibiting the virus-induced oxidative stress response and associated oxidative injury. The results of the present study support this concept by showing an elevated levels of MDA and the proinflammatory cytokine TNF-a upon dengue viral infection.…”