Studies on the in vitro phototoxicity of the antidiabetes drug glipizide.
The phototoxic antidiabetes drug glipizide (1) is photolabile under aerobic conditions and UV-B light. Irradiation of a phosphate-buffered solution of 1 under oxygen atmosphere produces 4 photoproducts as well as singlet oxygen, which was detected by trapping it with 2,5-dimethylfuran and by the histidine test. The photochemistry of 1 involves cleavage of the sulfonamine and the sulfonamine-R bonds. Red blood cell lysis, photosensitized by glipizide and the products of its aerobic photolysis were demonstrated. The photohemolysis rate was lower for 1 than for its photoproducts. Inhibition of this process on addition of 1, 4-diazabicyclo[2.2.2]octane (DABCO), reduced glutathione (GSH), Vitamin C, sodium azide, superoxide dismutase, and a-tocopherol confirmed the possibility of singlet oxygen, superoxide ion and free radicals participation. Furthermore, in a lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of glipizide was also verified. A low decreasing cell viability of lymphocytes and neutrophils was observed.
Vargas
F
F
Laboratorio de Fotoquímica, Centro de Quíimica, Instituto Venezolano de Insvestigaciones Científicas, I.V.I.C., Apartado 21827, Caracas Venezuela. fvargas@ivic.ivic.ve
Méndez
H
H
Tropper
E
E
Velázquez
M
M
Fraile
G
G
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005913:Glipizide / Q000378:metabolism / Q000528:radiation effects* / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000528:radiation effects* / Q000633:toxicity*; D007700:Kinetics; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D010782:Photolysis / Q000528:radiation effects*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen; D013053:Spectrophotometry; D014466:Ultraviolet Rays
D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D017319:Photosensitizing Agents; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D019787:Linoleic Acid; D010100:Oxygen; D005913:Glipizide