Indole-3-propionate: a potent hydroxyl radical scavenger in rat brain.
The hydroxyl radical scavenging activity of indole-3-propionate was evaluated by kinetic competition studies with the hydroxyl radical trapping reagent 2,2'-azino-bis-(3-ethyl-benz-thiazoline-6-sulfonic acid) (ABTS) and by measuring hydroxyl radical-initiated lipid peroxidation in the rat striatum. Using ABTS, the indole was shown to act as a potent hydroxyl radical scavenger with a rate constant of 7.8x1010 mol l-1 s-1. Hydroxyl radical-initiated lipid peroxidation, determined by measuring tissue malondialdehyde formation, was inhibited dose-dependently both in vitro and in vivo. Indole-3-propionate reacts with hydroxyl radicals at a diffusion controlled rate and can thereby provide on-site protection against the oxidative damage of biomolecules induced by these highly reactive and toxic oxygen intermediates. While it remains to be established if endogenous brain tissue levels of indole-3-propionate are sufficiently high to have a significant impact on total antioxidative capacity, the compound itself or a structurally related agent may be useful as an antioxidant adjuvant to combat hydroxyl radical-mediated oxidative stress.
Poeggeler
B
B
Maryland Psychiatric Research, Center University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USA.
Pappolla
M A
MA
Hardeland
R
R
Rassoulpour
A
A
Hodgkins
P S
PS
Guidetti
P
P
Schwarcz
R
R
D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism*; D002412:Cations / Q000037:antagonists & inhibitors; D003342:Corpus Striatum / Q000187:drug effects; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D017665:Hydroxyl Radical / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013451:Sulfonic Acids / Q000037:antagonists & inhibitors
D052160:Benzothiazoles; D002412:Cations; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D007211:Indoles; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D017665:Hydroxyl Radical; C008122:indol-3-yl pyruvic acid; C015292:indolepropionic acid