Characterization of novel furan compounds on the basis of their radical scavenging activity and cytoprotective effects against glutamate- and lipopolysaccharide-induced insults.
There is increasing evidence indicating that free radicals and oxygenases such as cyclooxygenase (COX) and lipoxygenase (LOX) are related to the onset and development of neurodegenerative diseases. In order to prevent and/or delay these diseases, the use of radical-scavenging antioxidants and inhibitors against oxygenases has received much attention. In the present study, we examined the radical-scavenging activity and cytoprotective effects of some novel furan compounds with potent inhibitory activity against oxygenases such as COX-1, COX-2, and 5-LOX. The radical-scavenging activity was assessed by studying the bleaching of beta-carotene by free radicals generated from an azo initiator. In this assay system, the rate constants for scavenging peroxyl radicals by furan S and furan L was estimated to be 2 x 10(4) and 3 x 10(4) M(-1) s(-1), respectively. We also investigated the cytoprotective effects of these compounds against cell death induced by several toxins. We found that the furan compounds exhibited cytoprotective effects against PC12 cell death induced by linoleic acid hydroperoxide, primary neuronal cell death induced by glutamate, and cell death induced by lipopolysaccharide. These results suggest the beneficial effects of the furan compounds against disorders related to glutamate and lipopolysaccharide.
Nishio
Keiko
K
Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
Fukuhara
Akiko
A
Omata
Yo
Y
Saito
Yoshiro
Y
Yamaguchi
Shuuhei
S
Kato
Hisatoyo
H
Yoshida
Yasukazu
Y
Niki
Etsuo
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D019610:Cytoprotection; D016166:Free Radical Scavengers / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism / Q000633:toxicity*; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014815:Vitamins / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D005663:Furans; D005971:Glutamates; D008070:Lipopolysaccharides; D014815:Vitamins; D019207:beta Carotene