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Protective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activity.

 Kyung Ahn  ;  Samin Hong  ;  Yu Mi Park  ;  Ja Yong Choi  ;  Won Taek Lee  ;  Kyung Ah Park  ;  Jong Eun Lee 
 Life Sciences, Vol.91(25-26) : 1345-1350, 2012 
Journal Title
 Life Sciences 
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AIMS: Proinflammatory factors released from activated microglia contribute to maintaining homeostasis against various noxious stimuli in the central nervous system. If excessive, however, they may initiate a pathologic neuroinflammatory process. In this investigation, we evaluated whether agmatine, a primary polyamine known to protect neurons, reduces lipopolysaccharide (LPS)-induced damage to microglia in vitro and in vivo. MAIN METHODS: For in vitro study, BV2-immortalized murine microglia were exposed to LPS with agmatine treatment. After 24hours, cell viability and the amount of nitrite generated were determined. For in vivo study, LPS was microinjected into the corpus callosum of adult male albino mice. Agmatine was intraperitoneally administered at the time of injury. Brains were evaluated 24hours after LPS microinjection to check for immunoreactivity with a microglial marker of ionized calcium binding adaptor molecule 1 (Iba1) and inducible nitric oxide synthase (iNOS). Using western blot analysis, protein expression of iNOS as well as that of the proinflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was determined. KEY FINDINGS: Agmatine significantly reduced the LPS-induced BV2 microglial cytotoxicity from over 80% to less than 60% (p<0.001), as determined by lactate dehydrogenase assay. It suppressed the nitrite production from 16.4±3.14μM to 5.5±1.27μM (p<0.001), as measured using the Griess reaction. Agmatine also decreased the activities of microglia and iNOS induced by LPS microinjection into corpus callosum. SIGNIFICANCE: Our findings reveal that agmatine attenuates LPS-induced microglial damage and suggest that agmatine may serve as a novel therapeutic strategy for neuroinflammatory diseases.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실)
Yonsei Authors
박경아(Park, Kyung Ah) ; 이원택(Lee, Won Taek) ; 이종은(Lee, Jong Eun) ; 홍사민(Hong, Sa Min)
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