Photochemical reactions and phototoxicity of sterols: Novel self-perpetuating mechanism for lipid photooxidation

Sterols are important lipid components that may contribute to phototoxicity. We have found that phototoxic response in earthworms is related to sterols extractable with lipophilic solvents, The photochemically active compounds in worm lipids are 5,7,9(11),22-ergostatetraen-3 beta-ol (9-DHE) and 5,7,9(11)-cholestatrien-3 beta-ol (9-DDHC), respectively. Human skin lipids art: known to contain 9-DHE, We have also found 9-DDHC in human skin, which is reported here for the first rime, In the presence of an excess of the corresponding 5,7-dienes (ergosterol or 7-dehydrocholesterol), these photoactive sterols constitute a self-regenerating source of singlet molecular oxygen (O-1(2) during irradiation in vivo or in vitro with UVA (315-400 nm), The quantum yield for photosensitization of O-1(2) by 9-DHE was Estimated to be 0,09. The O-1(2), is scavenged by the dienes and the rate constant for O-1(2) quenching by ergosterol was found to be 1.2 X 10(7) M-1 s(-1) in methyl t-butyl ether (MTBE). This scavenging ultimately leads to the production of 5,8-endo-peroxide and hydrogen peroxide, Photochemically induced superoxide radical was also produced on irradiation of sterol 5,7,9-trienes and trapped with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The production of singlet oxygen, peroxides and radicals by the sterols map be significant in the cell damaging and tumor promoting action of WA light on skin.