PREVENTION OF SINGLET OXYGEN-INDUCED DNA DAMAGE BY LIPOATE

Among the several biologically and pharmacologically active sulfur compounds examined, only lipoic acid and dihydrolipoic acid provided protection to plasmid DNA against singlet molecular oxygen (O-1(2)). O-1(2) was generated in phosphate buffer by the thermal dissociation of the endoperoxide of 3,3-(1,4-naphthylidene) dipropionate (NDPO2). The protecting effect of lipoic acid was time- and pH-dependent and significant protection was seen even at 50 muM. The antioxidant effect was adversely affected by temperatures above 45-degrees-C. Superoxide dismutase and catalase marginally enhanced this effect. Metal chelation with EDTA decreased the protection by lipoate, indicating that metal ions my be involved. The protective effect was diminished when the disulfide was added after single-strand breaks were induced by O-1(2). The formation of 8-oxoguanosine from guanosine upon exposure to NDPO2 was not altered by lipoate.