Lipid peroxidation, DNA damage, and apoptosis in dengue fever

Abstract

Interplay between the apoptosis, DNA damage, and oxidative stress as a host response to dengue viral infections remains unclear. Peripheral blood mononuclear cells (PBMCs) were isolated from 60 dengue infected patients, 20 patients with febrile illness other than dengue (OFI) and 10 non-febrile illness (NFI) patients. DNA damage in the PBMCs was assessed using single cell gel electrophoresis and stages of apoptosis underwent by the PBMCs were studied by Annexin-PI staining using flow cytometry. Plasma levels of malondialdehyde levels were estimated using thiobarbituric acid assay. Dengue infected individuals had showed increased DNA damage than NFI and OFI controls at the time of admission. Annexin-PI staining revealed increased frequency of apoptotic cells in dengue infected PBMCs than controls during the admission time. Similar pattern was observed in samples collected around defervescence. Within the dengue cases, percentage of live cells was higher in non-severe dengue than severe dengue at both the time points. Follow-up samples in dengue showed less number of live cells and higher percentage of apoptotic cells with respect to their baseline and this was reversed in case of OFI. Plasma malondialdehyde levels were found to be relatively higher in dengue cases than controls at admission and around defervescence. Significant positive correlation between DNA damage, apoptosis, and plasma malondialdehyde levels might pave a way for understanding the complex interactions between virus and hosts response thereby aids in identifying plausible immunopathological links contributing to disease pathogenesis. © 2018 IUBMB Life, 70(11):1133-1143, 2018.

Crocetin Improves Dengue Virus-Induced Liver Injury

“…The interplay between apoptosis and oxidative stress in the liver of severe DENV-infected patients was correlated with DENV-associated disease pathogenesis and disease severity [ 50 ]. In DENV-infected dendritic cells, regulating the cellular oxidative stress responses was reported to modulate DENV-induced apoptosis [ 46 ].…”

Serum lipid profile as a predictor of dengue severity: A systematic review and meta‐analysis

“…38 Recent evidence also shows that pro-inflammatory and oxidative factors activated by DENV induce degradation and reduce the release of cholesterol from synthesis site, contributing to its reduced serum levels. [39][40][41][42] Tumor necrosis factor (TNF)-α administration (16.7 μg/ 100 g of body weight) decreases serum total-cholesterol levels in Syrian hamster, probably due to reduced plasma activity of lecithin:cholesterol acyltransferase (LCAT). 39 Furthermore, an in vitro study has shown that IL-1β and IL-6 decrease cholesterol levels and apoB secretion from HepG2 cells, as well as increase LDLr mRNA levels and stimulate cholesterol catabolism in these cells.…”

“…Furthermore, lipids are highly susceptible to degradation by free radicals, and infection by DENV considerably elevates the overall oxidative state of the host. 41 When cholesterol is oxidized to cholest-4-ene-3- As shown by subgroup analysis, three factors influenced the association between serum cholesterol levels and dengue severity, such as ethical-racial differences, age range, and study design. The association demonstrated in the present review is significantly stronger among Asians (P-value <.0001) compared with Latin Americans (P-value = .01).…”

“…Recent evidence also shows that pro‐inflammatory and oxidative factors activated by DENV induce degradation and reduce the release of cholesterol from synthesis site, contributing to its reduced serum levels . Tumor necrosis factor (TNF)‐α administration (16.7 μg/100 g of body weight) decreases serum total‐cholesterol levels in Syrian hamster, probably due to reduced plasma activity of lecithin:cholesterol acyltransferase (LCAT) .…”

“…These results suggest that the actions of these cytokines on lipid metabolism may be involved in the decreased cholesterol levels in patients with severe dengue. Furthermore, lipids are highly susceptible to degradation by free radicals, and infection by DENV considerably elevates the overall oxidative state of the host . When cholesterol is oxidized to cholest‐4‐ene‐3‐one, it cannot be detected by enzymatic‐colorimetric methods, thus effectively reducing the detectable form of this lipid fraction in the plasma of dengue patients …”