D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant.
J Pharmacol Exp Ther
; 298(1): 103-9, 2001 Jul.
Article
em En
| MEDLINE
| ID: mdl-11408530
ABSTRACT
Tricyclodecan-9-yl-xanthogenate (D609) has been extensively studied in biological systems and exhibits a variety of biological functions, including antiviral, antitumor, and anti-inflammatory activities. Most of these activities have been largely attributed to the inhibitory effect of D609 on phosphatidylcholine-specific phospholipase C. However, as a xanthate derivative, D609 is a strong electrolyte and readily dissociates to xanthate anions and cations of alkali metals in solution. Xanthate anions and protonated xanthic acid contain a free thiol moiety and are highly reductive. This implies that D609 and other xanthate derivatives may function as potent antioxidants. Indeed, we found that D609 inhibited the Fenton reaction-induced oxidation of dihydrorhodamine 123 in a dose-dependent manner similar to that of pyrrolidinedithiocarbamate, a well known antioxidant. In addition, D609 inhibited the formation of the alpha-phenyl-tert-butylnitrone-free radical spin adducts and lipid peroxidation of synaptosomal membranes by the Fenton reagents. Furthermore, preincubation of lymphocytes with D609 resulted in a significant diminution of ionizing radiation (IR)-induced 1) production of reactive oxygen species; 2) decrease in intracellular reduced glutathione; 3) oxidative damage to proteins and lipids; and 4) activation of nuclear factor-kappaB. Moreover, when D609 (50 mg/kg i.v.) was administered to mice 10 min prior to total body IR (6.5 and 8.5 Gy), it protected the mice from IR-induced lethality. Thus, these results indicate that D609 is a potent antioxidant and has the ability to inhibit IR-induced cellular oxidative stress.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
Tionas
/
Hidrocarbonetos Aromáticos com Pontes
/
Linfócitos
/
Peroxidação de Lipídeos
/
Estresse Oxidativo
/
Antioxidantes
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article