Tumour necrosis factor alpha (TNF- ) stimulation of cells with established dengue virus type 2 infection induces cell death that is accompanied by a reduced ability of TNF-  to activate nuclear factor  B and reduced sphingosine kinase-1 activity

Influence of L-arginine on Cisplatin-Induced Hepatotoxicity in both normally Fed and Protein Malnourished Rats

“…These results supported by the study of Obima [45]. The elevation in serum AST and ALT levels due to PM may be caused by up regulation of the tumor necrosis factor (TNF) in the serum and of the absolute amounts of TNF secreted by cells, leading to an increase in the rate of cell damage as a consequence of PM [46]. This study showed that a significant increase in serum MDA and reduction in SOD, GSH and albumin levels were observed in the PM rats compared to the NF rats.…”

Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

“…S1P has important effects on immune cell migration, release of inflammatory mediators, phagocytosis and cell death, as reviewed by Carr et al 34 and Maceyka et al 35 Specific data concerning alterations in sphingolipid metabolism in dengue infection are scarce. In vitro, reduced SphK1 in dengue-infected cells showed enhanced TNF-a induced apoptosis, 24 which could limit severe complications induced by pro-inflammatory cytokines and limit ongoing viral replication within infected cells. SphK1 was also suggested to block type 1 IFN signaling as reviewed by Seo et al, 36 which plays a central role in anti-viral host defense.…”

“…Indeed, in vitro studies indicate that different dengue-exposed cell types had reduced SphK1 activity. 24,25 Moreover, endothelial cells contribute to plasma S1P levels 9 and the endothelial activation and dysfunction that occur in dengue infection 3 may therefore affect extracellular S1P concentrations by altering intracellular sphingolipid metabolism. While in vivo data of SphK1 or S1P lyase during human dengue infection have not yet been reported to the best of our knowledge, adult dengue patients from Singapore had increased sphingomyelin concentrations early in dengue infection.…”

The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication

“…1A). Further, DENV-induced apoptosis of transformed cell lines is associated with perturbations in ceramide homeostasis (33)(34)(35)59), and replication membranes isolated from a DENV-2-infected mosquito cell line are enriched with long-chain ceramides and dihydroceramides (32). We therefore investigated the effects of long-chain ceramides and dihydroceramides on DENV-2 replication, and we asked whether the antiviral activity of 4-HPR may be due to its effects on ceramide homeostasis.…”

“…4-HPR is a synthetic retinoid that alters ceramide homeostasis via the activation of serine palmitoyltransferase and ceramide synthase (29,30) and the inhibition of dihydroceramide desaturase (31). Ceramides and ceramide metabolism have been implicated in DENV replication (32) and DENV-induced apoptosis (33)(34)(35), making 4-HPR an attractive antiviral molecule that interacts with known lipid pathways important for DENV infection. Additionally, 4-HPR has been investigated in the clinic as a potential treatment or preventative agent for various cancers (36,37), psoriasis (38), obesity-associated insulin resistance (39), and macular degeneration (40).…”