Photogeneration of 3beta-hydroxy-5alpha-cholest-6-ene-5-hydroperoxide in rat skin: evidence for occurrence of singlet oxygen in vivo.
We identified singlet oxygen adduct of cholesterol, 3beta-hydroxy-5alpha-cholest-6-ene-5-hydroperoxide (5alpha-OOH), in skin of rats pretreated with oral doses of pheophorbide a and subsequent visible irradiation, that have been known to induce photosensitive diseases in animals and humans. In a living animal body, this is the first demonstration of presence of 5alpha-OOH, that is known to be formed exclusively by reaction in vitro between singlet oxygen and cholesterol. By the quantitative determination with high performance liquid chromatography equipped with a chemiluminescence detector, we observed time-dependent increase in concentrations of 5alpha-OOH in skin of rats pretreated with oral doses of pheophorbide a and subsequent visible irradiation, suggesting the occurrence of a labile activated oxygen species, singlet oxygen, in this system.
Yamazaki
S
S
Toxicology and Efficacy Research, Tsukuba Research Laboratories, Pharmacia & Upjohn, Ltd., Ibaraki, Japan. shinji.yamazaki@am.pnu.com
Ozawa
N
N
Hiratsuka
A
A
Watabe
T
T
D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004355:Drug Stability; D016014:Linear Models; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D008054:Lipid Peroxides; D017319:Photosensitizing Agents; D002734:Chlorophyll; C002843:cholesterol hydroperoxide; D002784:Cholesterol; C032623:pheophorbide a