Inhibition of lens opacification in x-irradiated rats treated with WR-77913. 1986

T B Osgood, and T W Menard, and J I Clark, and K A Krohn

Radiation induced cataracts are models for studying mechanisms of lens opacification. WR-77913, S-3-(amino-2-hydroxypropyl) phosphorothioate (NCS-318809), has been identified as a radioprotective agent. Injection of WR-77913 (1160 mg/kg, i.p.) 15 to 30 min before exposure to 15.3 gray of x-irradiation inhibited rat lenses from developing radiation cataracts. Irradiated rats which did not receive the drug developed dense cataracts. Lenses from control rats which received no radiation remained transparent. Individual lenses were weighed, homogenized, and assayed for protein content using the Lowry method. The molecular weight distribution of soluble protein was determined by HPLC. Mean lens weights were: controls 48.2 mg; irradiated, drug-treated 45.9 mg; and irradiated, nontreated 45.5 mg. Protein accounted for over 40% of the lens weight in control and drug-treated rats and less than 20% for the nontreated cataractous lenses. Water was less than 60% of the lens weight in control and drug-treated rats and over 80% in cataractous lenses. Insoluble protein ranged from 12 to 17% of the total lens weight for each group. The ratio of insoluble to soluble lens protein was 0.40 for control, 0.65 for drug-treated, and 11.28 for cataractous rat lenses. HPLC confirmed a dramatic loss of soluble protein and a complete absence of protein below 25K daltons in cataractous lenses. Proteins below 25K daltons accounted for over 25% of the soluble protein in control and drug-treated rat lenses. WR-77913 stabilizes protein composition and appears to be an effective inhibitor of radiation cataractogenesis.

UI MeSH Term Description Entries
D007908 Lens, Crystalline A transparent, biconvex structure of the EYE, enclosed in a capsule and situated behind the IRIS and in front of the vitreous humor (VITREOUS BODY). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the CILIARY BODY is crucial for OCULAR ACCOMMODATION. Eye Lens,Lens, Eye,Crystalline Lens
D008297 Male Males
D009946 Organothiophosphorus Compounds Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES. Compounds, Organothiophosphorus
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D010781 Photography Method of making images on a sensitized surface by exposure to light or other radiant energy. Photographies
D011833 Radiation Injuries, Experimental Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals. Experimental Radiation Injuries,Injuries, Experimental Radiation,Experimental Radiation Injury,Radiation Injury, Experimental
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001834 Body Water Fluids composed mainly of water found within the body. Water, Body
D002386 Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed) Cataract, Membranous,Lens Opacities,Pseudoaphakia,Cataracts,Cataracts, Membranous,Lens Opacity,Membranous Cataract,Membranous Cataracts,Opacities, Lens,Opacity, Lens,Pseudoaphakias
D003459 Crystallins A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses. Lens Proteins,Crystallin,Eye Lens Protein,Lens Protein, Eye,Protein, Eye Lens,Proteins, Lens

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