Photochemical Reactions and Phototoxicity of Sterols: Novel Self‐perpetuating Mechanism for Lipid Photooxidation

Abstract

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)-cholestartien-3 beta-ol (9-DDHC), respectively. Human skin lipids are known to contain 9-DHE. We have also found 9-DDHC in human skin, which is reported here for the first time. In the presence of an excess of the corresponding 5,7-dienes (ergosterol of 7-dehydrocholesterol), these photoactive sterols constitute a self-regenerating source of singlet molecular oxygen (1O2) during irradiation in vivo or in vitro with UVA (315-400 nm). The quantum yield for photosensitization of 1O2 by 9-DHE was estimated to be 0.09. The 1O2 is scavenged by the dienes and the rate constant for 1O2 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-endoperoxide 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 may be significant in the cell damaging and tumor promoting action of UVA light on skin.

Novel oxysterols observed in tissues and fluids of AY9944-treated rats: a model for Smith-Lemli-Opitz syndrome

“…As 7-DHC photooxidation yields a hydroperoxide and an endoperoxide as the primary products ( Fig. 4 ) ( 49,50 ), reaction of these peroxides with transition metal ions, such as those of iron and copper, can in turn promote the formation of secondary free radical oxidation products derived therefrom.…”

“…4 ) ( 49,50 ), in plasma of a SLOS patient may be based on ex vivo artifact. This fi nding also emphasizes the importance of handling samples from SLOS patients under dark or dim red-light conditions and/or under an atmosphere of inert gas.…”

“…1A ) was confi rmed to be one of the 7-DHC photooxidation products, 5 ( Fig. 4 ), by comparing the mass spectrum, 1 H-NMR and HSQC NMR spectra with those of a synthetic standard ( 49,50 ). However, formation of EnP (5,8) can be minimized (but cannot be completely avoided) when the brain samples were processed under dim red light, suggesting that this oxysterol is an ex vivo oxidation product.…”

Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome

“…Benzene (HPLC grade) was passed through a column of neutral alumina and stored over molecular sieves. Hexanes, ethyl acetate, methylene chloride, and methanol (all by guest, on www.jlr.org photooxidation products 13-15 were prepared as reported ( 42,43 ).…”

Potential Use of Spin Traps to Control ROS in Antipollution Cosmetics—A Review

“…After UV-A irradiation absorption, endogenous photosensitizes such as flavins [45], NADH/ NADPH [46], urocanic acid [47], and some sterols [48] present in tissue are converted to their long-lived triplet state, which in turn can transfer energy to oxygen molecules to form an energetically excited and highly reactive singlet oxygen. Additionally, a novel class of UV-A photo-sensitizers comprised of skin biomolecules based on 3-hydroxypyridine derivatives such as enzymatic collagen cross-links, B6 vitamin, and glycation end products in chronologically aged skin are capable of skin photooxidative damage [49].…”