In vitro metabolism study of edaravone in Wistar and hairless rat skin.
We investigated the skin metabolism of edaravone as a radical scavenger in Wistar and hairless rat skin. Approximately 1 g of abdominal skin was excised from 10-week-old Wistar and hairless rats, homogenized in 10 ml saline, and centrifuged at 10000 g for 20 min. The supernatant fluid was used for the examination of edaravone metabolism in the skin, and we also used supernatant fluid that was heated at 80 degrees C. Edaravone solution (0.05 ml, 2.4 micromol/ml) was added to 0.95 ml Wistar rat and hairless rat skin homogenate supernatant fluids. In Wistar rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5, 10, 20 and 30 min was 61.58+/-1.65, 41.84+/-8.52, 35.54+/-8.62, 19.73+/-5.99 and 13.89+/-4.40%, respectively. In hairless rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5 and 10 min was 50.19+/-14.17, 6.71+/-5.82 and 0.89+/-0.80%, respectively, and edaravone was not detected after 20 min. Although it was thought that metabolic enzyme activity in skin homogenate supernatant fluid was lost following heat treatment at 80 degrees C, the residual amount of edaravone in our skin homogenate supernatant fluid decreased with time. It is suggested that edaravone metabolism in the skin is necessary for non-enzymatic reactions.
Research & Development Division, Mikasa Seiyaku Co., Ltd., Toyotama-Kita, Tokyo, Japan.
Toshiaki
T
Sato
Keizo
K
Mizuno
Fumiyoshi
F
Ishii
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D054772:Rats, Hairless; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine