Inhibition of erythrocyte lipid peroxidation and hemolysis by the radioprotectant WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid
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), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ERYTHROCYTES
HEMOLYSIS
LIPIDS
METABOLISM
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
BIOLOGICAL MODELS
DNA
HYDROGEN PEROXIDE
INHIBITION
RATS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DRUGS
HYDROGEN COMPOUNDS
LYSIS
MAMMALS
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PEROXIDES
RODENTS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture