Platelet-activating factor (1-O-acyl sn2-acetyl sn-glycero-3-phosphocholine, PAF), an ether-linked phospholipid produced by many cells of the innate immune system in response to multiple inflammatory and allergic stimuli. PAF is continuously synthesized by many cells type at a lower amount and this activity is regulated by Platelet-activating factor Acetylhydrolase(PAF-AH), a catabolic enzyme for PAF. PAF has diverse physiological action on different organs and isolated cells, and activate at a sub-nanomolar concentration (10-9 to 10-12 M).
The biological action of PAF is exerted by binding to a unique G-protein-coupled receptor (PAF-R), which is ubiquitously expressed on the surface immune cells. PAF-R signaling trigger many events, including platelet aggregation, chemotaxis, reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, bronchoconstriction, vascular permeability and synthesis of various lipid-mediator such as eicosanoids. Many clinical studies have been reported, PAF associated with many pathological conditions such as sepsis, cancer, asthma, rheumatoid arthritis and inflammatory diseases. In addition, blocking PAF- R signaling with WEB-2086 ( A PAF-R antagonist) inhibits LPS-induced TNF-alpha production ex vivo studies. Furthermore, circulatory PAF was elevated in inflammatory and liver disease. For example, a higher level hepatic and circulatory PAF was found in cirrhosis.
Oxidative stress is an abnormal situation, where an imbalance between prooxidants and antioxidants. Several clinical studies have described the involvement of oxidative stress to be crucial in the progress of pathological conditions such as atherosclerosis(), arthritis(), heart failure(), Parkinson disease(), acute respiratory distress syndrome (ARDS)(), cancer() and sepsis(). In addition, superoxide anion reacts with nitric oxide to produces peroxynitrite. peroxynitrite able crosses the membrane and damage variety of biomolecules.
Normally, cell eliminates the excess of ROS by an antioxidant defense system and protected from oxidative stress. The Nrf2-ARE signaling is the most sensitive pathway to oxidative stress and this event causes the transcription of the antioxidant enzymes such as catalase, superoxide oxide dismutase, glutathione S-transferase, heme oxygenase-1 and NADPH-quinine oxidase. Previous studies have shown that superfusion of rats with PAF causes oxidative stress and albumin leakage was attenuated by pre-treatment with catalase. Jacob sp reported that exogenous administration (i.p) PAF at concentration 5 microgram /mouse in Swiss albino mice causes sudden death (within 15 to 20min). Furthermore, pre-treatment with WEB-2086 and PAF-AH confers complete protection against PAF-induced lethality (). To understand the possible mechanism of PAF-induced mortality of Swiss albino mice, we pretreated animals with antioxidant vitamins( Vitamin C and Vitamin E), N-acetyl cysteine (NAC), Gallic acid and N?-Nitro-L-arginine(L-NNA), a nonspecific Nitric oxide synthase inhibitor().
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Antioxidants such as Vitamin C(50mg/kg), Vitamin E (200IU/kg), NAC(50mg/kg) and gallic acid(50mg/kg) partially protect the PAF-induced mortality in Swiss albino mice.
