Antioxidative property of T-0970, a new ureidophenol derivative.
We investigated the antioxidative property of T-0970, a newly synthesized ureidophenol derivative. The inhibitory effect of T-0970 on spontaneous lipid peroxidation in rat brain was 10 times greater than those of well-known antioxidants such as butylhydroxytoluene (BHT), probucol and alpha-tocopherol. T-0970 also showed dose-dependent free radical scavenging activities in vitro for both superoxide anions and hydroxyl radicals. The radical-scavenging potencies of T-0970 were about 10-30 times stronger than those of BHT. We evaluated the in vivo antioxidative ability of T-0970 in the animal model of acute oxidative tissue injury in rats. Intraperitoneal injection of ferric nitrilotriacetate (Fe/NTA) caused an acute and remarkable increase in the level of thiobarbituric acid-reactive substances (TBARS) in both plasma and the liver, and also resulted in a considerable elevation of the plasma levels of GOT and GPT indicative of hepatic injury. Both oral and intravenous administration of T-0970 dose-dependently depressed these diagnostic parameters. These results indicate that T-0970 may have a therapeutic potential in various diseases associated with oxidative tissue injury.
Suzumura
K
K
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan. suzumura@tanabe.co.jp
Hashimura
Y
Y
Kubota
H
H
Ohmizu
H
H
Suzuki
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D005290:Ferric Compounds / Q000633:toxicity; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000737:chemistry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D010636:Phenols; D010671:Phenylurea Compounds; D011725:Pyridines; C406666:T 0970; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D017665:Hydroxyl Radical; D014508:Urea; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D009571:Nitrilotriacetic Acid; D011341:Probucol; C020326:ferric nitrilotriacetate