Studies on the in vitro phototoxicity of the antidiabetes drug gliclazide

The phototoxic antidiabetes drug gliclazide (1) is photolabile under aerobic conditions and UV-B light. Irradiation of a phosphate buffered solution of 1 under oxygen atmosphere produces two photoproducts. The photochemistry of 1 involves cleavage of the S-N and C(O)-N bonds of the urea unit. Red blood cell lysis photosensitized by 1 was demonstrated. Their photoproducts didn't show this effect. Inhibition of this process by addition of DABCO, GSH, confirmed the possibility of the participation of free radicals in the photoinduced hemolysis. Furthermore, in a lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of gliclazide was also verified. The generation of singlet oxygen during the photolysis of gliclazide was ruled out by means of the histidine and NaN3 assays. In a supplementary study the ability of 1 to inhibit free radical or reactive oxygen species (OH, O2, H2O2) generated in cell-free systems was investigated using chemiluminescence and electronic absorption spectra.