INHIBITING EFFECTS OF ANTIOXIDANTS ON DRUG-INDUCED PHOTOTOXICITY IN CELL-CULTURES - INVESTIGATIONS WITH SULFONAMIDE-DERIVED ORAL ANTIDIABETICS AND DIURETICS

The sulphonamide-derived oral antidiabetics chlorpropamide, glibenclam ide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiaz ide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiaz ide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlo rmethiazide 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, pireta nide, polythiazide and trichlormethiazide. Bendroflumethiazide was pho totoxic at concentrations of 0.05 mM and above; bemetizide, benzylhydr ochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at concentrations of 0.25 mM or more; the oral antidiabetics glibenclamid e and gliquidone, as well as the diuretics butizide, hydrochlorothiazi de, piretanide, polythiazide and trichlormethiazide were phototoxic at concentrations of 0.5 mM. To evaluate the effects of antioxidants, as corbic acid, alpha-tocopherol, beta-carotene or ubiquinone was added t o the tissue culture flasks before irradiation. The phototoxic inhibit ion 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. (C) 1997 Elsevier S cience S.A.