PHOTOTOXICITY DUE TO SULFONAMIDE DERIVED ORAL ANTIDIABETICS AND DIURETICS - INVESTIGATIONS IN A CELL-CULTURE MODEL

A number of sulphonamide-derived oral antidiabetics (chlorpropamide, g libenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbuta mide) and diuretics (bemetizide, bendroflumethiazide, benzylhydrochlor othiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlor othiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, t richlormethiazide and xipamide) were investigated for phototoxicity in a cell culture model. Cell death dependent on ultraviolet A fluence a nd test substance concentration was observed in the presence of the or al antidiabetics glibenclamide and gliquidone, as well as the diuretic s bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetani de, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, pol ythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic a t 5x10(-5) M and higher concentrations, bemetizide, ben zylhydrochloro thiazide, bumetanide and hydroflumethiazide were phototoxic at 2.5x10( -4) M and higher concentrations, and the oral antidiabetics glibenclam ide and gliquidone as well as the diuretics butizide, hydrochlorothiaz ide, piretanide, polythiazide and trichlormethiazide were phototoxic a t 5(-4) M and higher concentrations. Electron microscopic investigatio ns showed swelling of mitochondria and endoplasmic reticulum as well a s aggregation of euchromatin when the cells were irradiated in the pre sence of photosensitizers