Drug-radiation interval as a variable in evaluating the mechanism of action of radiation cataract inhibition by WR77913
John C. Livesey: 0000-0001-9010-5970
Conference Title/Conference Publication
Association for Research in Vision and Ophthalmology, Annual Meeting
April 28-May 3, 1991
Date of Presentation
S-3-Amino-2-bydroxypropylphosphorothioic acid (WR77913) prevents or inhibits cataract development after whole head radiation in nus [Osgood et al., Invest. Ophthalmol. Vis. Sci. 27 (1986) 1780]. Metabolites of this drug are known to act in certain tissues as a radical scavenging agent, reducing radiation effects by fast radiation-chemical processes. In order to test the hypothesis that WR77913 is acting to prevent radiation damage in the lens by scavenging radiation-induced radicals, we examined the efficacy of the drug when given at several time intervals before or after whole head irradiation of six-week-old male Sprague-Dawley rats. Freshly prepared solutions of WR779I3 (8I5 mg/kg) were injected intraperitoneally into nus (N = 4- 6 per group) 14 days, 7 days, I day or 30 minutes prior to or 30 minutes, I day, 3 days or 7 days after 15 Gy of 137Cs y-irradiation delivered at a dose rate of 1 Gy/min. Rats were examined photobiomicroscopically at regular intervals after treatment and cataracts were staged according to the rating scale of Sasaki et al. (Ophthal. Res. 15 (1983) 185).
When drug was injected before the irradiation period, substantial delay in the appearance of cataract was observed. Cataract progression to Stage 4 was delayed from 6- 7 weeks in the radiation·only group to 24, 14, 16 or to >50 weeks if a single dose of WR77913 (815 mg/kg) was injected 14 days, 7 days, 1 day, or 30 minutes prior to irradiation, respectively. A modest delay was noted if a single injection of drug was administered 30 minutes after irradiation, while a single injection of the drug 1 day, 3 days, or 7 days after iradiation was without effect.
These results imply that the mechanism of action of the drug is not limited to fast radiation-chemical events occurring during the irradiation period, since the persistence of the drug 14 days after injection is unlikely. Rather, other biochemical or biological events must be invoked to explain this inhibition of cataractogenesis.
Livesey, John C. and Sadeghi, K. G., "Drug-radiation interval as a variable in evaluating the mechanism of action of radiation cataract inhibition by WR77913" (1991). School of Pharmacy and Health Sciences Faculty Presentations. 377.