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Abstract

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Molecular Mechanisms for Lipopolysaccharide-induced Biphasic Activation of Nuclear Factor-κB (NF-κB)

“…It is well known that PAF is an inducer of NF-B activation in vitro (22,23). Regarding the in vivo role of PAF in NF-B activation, our observations also suggest that PAF is a critical mediator in the early activation of NF-B (10,11,15) in a reactive oxygen intermediator-dependent manner (14). This early NF-B activity induced by PAF results in the expression of a variety of early response genes.…”

A novel mechanistic approach for the anti-fibrotic potential of rupatadine in rat liver via amendment of PAF/NF-ĸB p65/TGF-β1 and hedgehog/HIF-1α/VEGF trajectories

“…In the current investigation, DEN intoxication disrupted the redox balance in favor of increased ROS, which increases the hepatic content of PAF, as demonstrated earlier by Hwa Choi et al (2000) and Ajiboye et al (2013). On the other hand, RUP significantly prevented PAF activation, mainly through the inhibition of oxidative stress.…”

Protective Effect of Olive Oil Microconstituents in Atherosclerosis: Emphasis on PAF Implicated Atherosclerosis Theory

“…In addition, α-T at even higher concentrations (200 μM), reduced expression of intercellular adhesion molecule-1 (ICAM-1) and VCAM-1 on interleukin-1β (IL-1β)-stimulated endothelial cells as well as PAF-induced expression of the adhesion molecules, CD11b and CD18 on neutrophils [ 61 ]. Lastly, vitamin E, at final concentration 10 −4 M, inhibited the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) induced by PAF as well as the expression of tumor necrosis factor alpha (TNF-α) induced by NF-κB in a macrophage cell line [ 62 ].…”