TY - JOUR
T1 - Radioprotection against cataract formation by WR-77913 in gamma-irradiated rats
AU - Menard, Thomas W.
AU - Osgood, Thomas B.
AU - Clark, John I.
AU - Spence, Alexander M.
AU - Steele, Jeannette E.
AU - Krohn, Kenneth A.
AU - Livesey, John C.
N1 - Funding Information:
Radiation-induced cataract formation is a potentially serious sequelae of tumoricidal doses of conventional radiotherapy for ocular or head and neck tumors. Exposure to doses of 12 Gy or greater of photon radiation to the eye, frequently leads to progressive cataracts and subsequent visual impairment. The development of radiation-induced cataracts in rats is similar to those observed in humans.7 Radiation exposure to the eye is currently limited to lead shielding and beam field angulation. l2 Previous studies on the prevention of cataracts by cysteine and glutathione,i7 cystamine and AET (Zaminoethyliso-thiouronium)* showed a protective effect only at toxic or near toxic doses. Therefore, these compounds would ap- Presented at the Chemical Modifiers for Cancer Treatment Conference, Clearwater, Fl, 20-24 October 1985. * Dept. of Oral Medicine. 7 Dept. of Biological Structure. $ Dept. of Medicine (Neurology). $ Dept. of Radiology (Nuclear Medicine). ** Dept. of Radiation Oncology. This work was supported by NIH Grants CA-36485 and EY-04542.
PY - 1986/8
Y1 - 1986/8
N2 - 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 > total eye ≅ humor > 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.
AB - 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 > total eye ≅ humor > 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.
KW - Cataracts
KW - Radioprotectors
KW - WR-77913
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U2 - 10.1016/0360-3016(86)90199-9
DO - 10.1016/0360-3016(86)90199-9
M3 - Article
C2 - 3019964
AN - SCOPUS:0022460238
SN - 0360-3016
VL - 12
SP - 1483
EP - 1486
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
IS - 8
ER -