Radioprotection against cataract formation by WR-77913 in gamma-irradiated rats

Thomas W. Menard, Thomas B. Osgood, John I. Clark, Alexander M. Spence, Jeannette E. Steele, Kenneth Krohn, John C. Livesey

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1483-1486
Number of pages4
JournalInternational journal of radiation oncology, biology, physics
Volume12
Issue number8
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

cataracts
Cataract
Lenses
rats
lenses
Crystallins
animals
proteins
hydration
Pharmaceutical Preparations
drugs
Radiation
Crystalline Lens
Wit and Humor
irradiation
WR 77913
Intraperitoneal Injections
Head
High Pressure Liquid Chromatography
globes

Keywords

  • Cataracts
  • Radioprotectors
  • WR-77913

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Radioprotection against cataract formation by WR-77913 in gamma-irradiated rats. / Menard, Thomas W.; Osgood, Thomas B.; Clark, John I.; Spence, Alexander M.; Steele, Jeannette E.; Krohn, Kenneth; Livesey, John C.

In: International journal of radiation oncology, biology, physics, Vol. 12, No. 8, 1986, p. 1483-1486.

Research output: Contribution to journalArticle

Menard, Thomas W. ; Osgood, Thomas B. ; Clark, John I. ; Spence, Alexander M. ; Steele, Jeannette E. ; Krohn, Kenneth ; Livesey, John C. / Radioprotection against cataract formation by WR-77913 in gamma-irradiated rats. In: International journal of radiation oncology, biology, physics. 1986 ; Vol. 12, No. 8. pp. 1483-1486.
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