Inhibiting effects of antioxidants on drug-induced phototoxicity in cell cultures. Investigations with sulphonamide-derived oral antidiabetics and diuretics.
The sulphonamide-derived oral antidiabetics chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide were investigated for phototoxicity in a cell culture model. Cell death dependent on ultraviolet A (UVA) radiation fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at concentrations of 0.05 mM and above; bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at concentrations of 0.25 mM or more; the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at concentrations of 0.5 mM. To evaluate the effects of antioxidants, ascorbic acid, alpha-tocopherol, beta-carotene or ubiquinone was added to the tissue culture flasks before irradiation. The phototoxic inhibition of the colony-forming ability was largely reduced by the addition of ascorbic acid and alpha-tocopherole, indicating the involvement of reactive oxygen species in the phototoxic process.
Selvaag
E
E
Department of Dermatology, Ullevaal Hospital, University of Oslo, Norway.
Anholt
H
H
Moan
J
J
Thune
P
P
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D017484:Dermatitis, Phototoxic; D004232:Diuretics / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D004232:Diuretics; D007004:Hypoglycemic Agents; D013449:Sulfonamides; D014810:Vitamin E; D001205:Ascorbic Acid