Activity of a cationic carotenoid derivative in a mouse model of protoporphyria.
Prior work using cell culture has shown that certain synthetic carotenoid derivatives are more effective than natural carotenoids in preventing photosensitized cell killing. These carotenoid derivatives are either cationic or are weak bases. We have now found that of one of these derivatives, the Girard's reagent T derivative of beta-apo-8'-carotenal (GRT-carotenal) decreases acute photosensitivity in a mouse model of protoporphyria. When GRT-carotenal was added to the diet of SKH1 mice, both GRT-carotenal and its metabolites accumulated in the skin of the mice. Protoporphyria was induced in SKH1 mice by adding collidine to their diet. When the porphyric mice were exposed to 400 nm light (2.6+/-0.1 mW cm(-2)) for a period of 2h, the skin on the backs of these animals increased in thickness. Increased vascularity also developed in the skin of the mouse ears. Animals, that were fed a diet containing both collidine and GRT-carotenal and then exposed to light, had significantly smaller increases in skin thickness and less prominent increases in the vascular pattern on their ears.
Kanofsky
Jeffrey R
JR
Medical and Neurology Service Line, Edward Hines Jr., Department of Veterans Affairs Hospital, P.O. Box 278, Hines, IL 60141, USA. jeff.kanofsky@med.va.gov <jeff.kanofsky@med.va.gov>
Sima
Paul D
PD
D000818:Animals; D002338:Carotenoids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002412:Cations; D004195:Disease Models, Animal; D008027:Light / Q000009:adverse effects; D051379:Mice; D010787:Photosensitivity Disorders / Q000139:chemically induced / Q000188:drug therapy*; D011725:Pyridines; D016896:Treatment Outcome
D002412:Cations; C425083:GRP-carotenal; D011725:Pyridines; D002338:Carotenoids; C007106:gamma-collidine