In vitro studies of the phototoxic potential of the antidepressant drugs amitriptyline and imipramine.
Amitriptyline and imipramine, two tricyclic antidepressant drugs, have been studied to evaluate their phototoxic potential using various models. Reactive oxygen species production was investigated. A negligible production of singlet oxygen was observed for both compounds whereas a significant production of superoxide anion was noted for amitriptyline in particular. Moderate red blood cell lysis under UVA light (365 nm) was induced in the presence of the two drugs at a concentration of 50 microM. Cellular phototoxicity was investigated on a murine fibroblast cell line (3T3). The two drugs were phototoxic causing cell death at a concentration of 100 microM and a UVA dose in the range of 3.3-6.6 J/cm2. Furthermore, the two drugs photosensitized the peroxidation of linoleic acid, as monitored by the formation of dienic hydroperoxides. The presence of BHA and GSH, two free radical scavengers, significantly reduced the lipid oxidation photoinduced by the drugs, suggesting a predominant involvement of radical species. Finally, the involvement of nucleic acids in the phototoxicity mechanism was also investigated using a pBR322 plasmid DNA as a model.
Viola
G
G
Department of Pharmaceutical Sciences, University of Padua, Italy.
Miolo
G
G
Vedaldi
D
D
Dall'Acqua
F
F
D000639:Amitriptyline / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D017484:Dermatitis, Phototoxic / Q000209:etiology* / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D007099:Imipramine / Q000737:chemistry / Q000633:toxicity*; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010777:Photochemistry; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D014466:Ultraviolet Rays
D000929:Antidepressive Agents, Tricyclic; D004396:Coloring Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D000639:Amitriptyline; D004247:DNA; D019787:Linoleic Acid; C022616:thiazolyl blue; D007099:Imipramine