S-Allyl-L-cysteine attenuates cerebral ischemic injury by scavenging peroxynitrite and inhibiting the activity of extracellular signal-regulated kinase.
S-Allyl-L-cysteine (SAC) has been shown to reduce ischemic injury due to its antioxidant activity. However, the antioxidant property of SAC has been controversial. The present study investigated the neuroprotective mechanism of SAC in cerebral ischemic insults. SAC decreased the size of infarction after transient or global ischemic insults. While it did not alter the N-methyl-D-aspartate excitotoxicity, SAC significantly scavenged the endogenously or exogenously produced ONOO- and reduced ONOO- cytotoxicity. In contrast, SAC has much lower scavenging activity against H2O2, O2*(-) or NO. Further, SAC inhibited the activity of extracellular signal-regulated kinase (ERK) increased in cultured neurons exposed to oxygen-glucose deprivation or in rat brain tissue after transient middle cerebral artery occlusion. The neuroprotective effect of SAC was mimicked by the ERK inhibitor U0125. The present results indicate that SAC exert its neuroprotective effect by scavenging ONOO- and inhibiting the ERK signaling pathway activated during initial hypoxic/ischemic insults.
Kim
Ji-Myung
JM
Food Function Research Division, Korea Food Research Institute, Sungnam, South Korea.
Lee
Jae-Chul
JC
Chang
Namsoo
N
Chun
Hyang Sook
HS
Kim
Won-Ki
WK
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005849:Gerbillinae; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D004791:Enzyme Inhibitors; D030421:Peroxynitrous Acid; C065299:S-allylcysteine; D048049:Extracellular Signal-Regulated MAP Kinases; D003545:Cysteine