Protection by
WR-77913 against radiation-induced
cataract formation in rats was observed following intraperitoneal (i.p.) administration of
drug (1160 mg/kg) 15-30 min before exposure to 15.3 Gy of Cs-137 whole head irradiation. Control groups included irradiated, non-protected animals, and
sham-irradiated aging controls. Protection was documented photographically and by analysis of eye lens constituents. All non-protected irradiated animals developed dense
cataracts throughout the lens between 90-120 days post-irradiation, while
WR-77913 protected animals developed minimal lens opacification through 200 days post-irradiation. No opacification in aging controls was seen. Lens
protein analysis by Lowry assay and size exclusion HPLC showed radioprotected and aging control animals were similar in
protein content, distribution of total and soluble
protein, and degree of lens hydration. This contrasted significantly with cataractous
lenses of non-protected animals. In cataractous
lenses, the soluble
protein concentration in the 25-43 K dalton range was approximately 10% of that found in radioprotected or aging control
lenses. Hydration was substantially higher in cataractous lens. These results indicate that
WR-77913 protects against lens opacification,
protein insolubilization, and hydration in
lenses of irradiated animals. Biodistribution studies with [S-35]-
WR-77913 showed ocular uptake of
drug within 15 minutes after i.p. injection, which remained relatively constant through 60 min. The relative order of
drug concentration for individual eye components was: globe greater than total eye approximately equal to humor greater than lens. Although the mechanism of radioprotection observed remains to be elucidated,
WR-77913 clearly prevents radiation-induced
cataracts in rats. The potentially significant clinical use for this radioprotective compound is being investigated further.