In vivo and photophysical studies on photooxidative damage to lens proteins and their protection by radioprotectors.
Photooxidation, whether initiated by an endogenous or exogenous sensitizer, is an important mechanism in light induced damage to the lens. One of the substrates for this damage is lens protein. A porphyrin sensitizer which binds to lens proteins [mesotetra(p-sulfonatophenyl) porphyrin (TPPS)] was found to photooxidize Skh-2 pigmented mice lens protein in vivo. Uroporphyrin, a model for a non-binding photosensitizer, did not induce photooxidative damage to the mouse lens. The radioprotector 3-amino-2-hydroxypropyl phosphorothioate (WR-77913) was investigated as an agent to retard or negate in vivo photooxidative damage to the lens. Intraperitoneal injections of WR-77913 prior to irradiation reduced the TPPS induced photodestruction of lens protein in Skh-2 pigmented mice. The mechanism of protection was also investigated. Thiols were found to quench both the triplet state of porphyrins and the reactive intermediate singlet oxygen on the order of 10(5) and 10(6) M-1 s-1 respectively. These are probably not fast enough to explain most of the protection afforded by thiols. An additional mechanism may be the accelerated photobleaching of porphyrins by thiols which protects tissue by reducing the absorptions due to the porphyrins.
Roberts
J E
JE
Division of Science and Mathematics, Fordham University, New York, NY 10023.
Kinley
J S
JS
Young
A R
AR
Jenkins
G
G
Atherton
S J
SJ
Dillon
J
J
D004999:Amifostine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003459:Crystallins / Q000187:drug effects* / Q000528:radiation effects; D008027:Light; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D010777:Photochemistry; D011166:Porphyrins / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
D003459:Crystallins; D011166:Porphyrins; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C035284:WR 77913; D004999:Amifostine