Benzylhydrochlorothiazide

The NHIK 3025 cell line (Norsk Hydro Institutt for Kreftforskning), a human in situ carcinoma of the cervix cell line, was used to investigate the thiazides bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide for their potential phototoxic properties. Cell death following UVA irradiation and dependent on test substance concentration was observed in the presence of all the tested substances except chlortalidone, furosemide, indapamide and xipamide. Bendroflumethiazide was phototoxic at concentrations of 0.05 mM and higher; bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 0.25 mM and higher and butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 0.5 mM and higher.

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.