In vitro cross-linking of bovine lens proteins photosensitized by promazines.
Promazine derivatives induce cross-linking of bovine lens crystallins in vitro by irradiation with near-ultraviolet (UV) light in the presence of O2, as revealed by electrophoresis after denaturation. With the five derivatives tested (promazine [PZ], chlorpromazine [CPZ], triflupromazine [ TFPZ ], methoxypromazine [ MTPZ ], and acepromazine [ ACPZ ] ), single-hit kinetics are observed. Evidence implicating the cation radicals of the PZ derivatives as the causative agent of this in vitro effect is presented. Hydroxyl radicals do not appear to be involved in the photo-cross-linking reaction. Sodium ascorbate protects against damage induced either by PZ derivatives plus light or by PZ cation radicals in the dark. These findings are discussed with respect to development of cataracts induced by these drugs in vivo.
D000075:Acepromazine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002746:Chlorpromazine / Q000494:pharmacology; D003459:Crystallins / Q000378:metabolism* / Q000528:radiation effects; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology; D011395:Promazine / Q000494:pharmacology*; D014273:Triflupromazine / Q000494:pharmacology; D014466:Ultraviolet Rays
D003459:Crystallins; D005609:Free Radicals; D010640:Phenothiazines; D000075:Acepromazine; C008393:methopromazine; D011395:Promazine; D014273:Triflupromazine; D010100:Oxygen; D002746:Chlorpromazine