Changes in the levels of glutathione after cellular and cutaneous damage induced by squalene monohydroperoxide.
Squalene monohydroperoxide (Sq-OOH), the initial product of ultraviolet-peroxidated squalene, was used to investigate the effect of peroxidative challenge upon the glutathione contents in rabbit ear skin and primary-cultured fibroblasts derived from rabbit ear skin. The cellular reduced glutathione (GSH) contents decreased during 30-minute incubations in vitro with Sq-OOH, and oxidized glutathione (GSSG) was formed concomitantly, indicating that Sq-OOH had a potential for GSH-depleting activity in vitro. When Sq-OOH was applied topically to the skin in vivo, only GSSG contents increased significantly within 30 minutes. Moreover, pretreatment with the GSH depletors, DL-buthionine sulfoximine (BSO) and diethyl maleate (DEM), could potentiate the cytotoxicity and comedogenicity induced by Sq-OOH. These findings suggest that the endogenous antioxidant, glutathione, is quite sensitive to Sq-OOH and may be an important material for protecting cells and/or tissues against the oxidative stress induced by Sq-OOH treatment.
Chiba
K
K
Department of Toxicology, Safety Research Center, Yakult Central Institute for Microbiological Research, 1796 Kunitachi-shi-yaho, Tokyo, 186-8650, Japan. katsuyoshi-chiba@yakult.co.jp
Yoshizawa
K
K
Makino
I
I
Kawakami
K
K
Onoue
M
M
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D008298:Maleates / Q000494:pharmacology; D010545:Peroxides / Q000633:toxicity*; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013185:Squalene / Q000633:toxicity*
D008298:Maleates; D010545:Peroxides; D011838:Radiation-Sensitizing Agents; D019328:Buthionine Sulfoximine; D013185:Squalene; C014476:diethyl maleate; D005978:Glutathione