Inhibition of erythrocyte lipid peroxidation and hemolysis by the radioprotectant WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid

Journal Article · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7187866

Sancho, A M; Kumar, K S; Vaishnav, Y N; Weiss, J F

Chemical radioprotection is often interpreted in terms of protection or repair of DNA damaged predominantly by reactive oxygen species formed from the radiolysis of water. Radiation injury can also be related to membrane damage as a consequence, e.g., of lipid hydroperoxide formation, but the role of lipid peroxidation in radioprotection has not been studied widely. The authors have used red cell model systems in this regard, which have the advantage of lack of organelles and DNA, and the potential for characterizing factors that influence drug uptake. Cumene hydroperoxide (CHP) was used to mimic radiation-induced hydroperoxides. After 2.5 hr incubation of rat erythrocytes with 1.0 mM CHP, 20% hemolysis was observed, which appeared to be related to glucose depletion in the cells, since the presence of glucose (5mM) inhibited hemolysis. Hemolysis was also totally inhibited by 5 mM WR-2721. Thiobarbituric acid-reactive substances (indicative of lipid peroxidation) were detectable before hemolysis and inhibited by WR-2721. WR-2721 and its free sulfhydryl form (WR-1065) were also capable of inhibiting radiation-induced formation of pentane in erythrocyte ghost preparations. These data indicate that the antioxidant action of WR-2721 is due to its conversion to WR-1065, and this antioxidant effect may contribute to the radioprotective effect of the drug.

• Research Organization: Armed Forces Radiobiology Research Institute, Bethesda, MD
• OSTI ID: 7187866
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY FLUIDS
DNA
DRUGS
ERYTHROCYTES
HEMOLYSIS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
INHIBITION
LIPIDS
LYSIS
MAMMALS
MATERIALS
METABOLISM
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PEROXIDES
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RATS
RODENTS
VERTEBRATES