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. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:150–158, 2001

[1]  M. Onoue,et al.  Comedogenicity of squalene monohydroperoxide in the skin after topical application. , 2000, The Journal of toxicological sciences.

[2]  T. Sone,et al.  Skin roughness and wrinkle formation induced by repeated application of squalenemonohydroperoxide to the hairless mouse , 1999, Experimental dermatology.

[3]  J. Hayes,et al.  Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. , 1999, Free radical research.

[4]  A. Kligman,et al.  Carcinogens show comedogenic activity: a potential animal screen for tumorigenic substances. , 1994, Cancer letters.

[5]  L. Packer,et al.  Recovery of antioxidants and reduction in lipid hydroperoxides in murine epidermis and dermis after acute ultraviolet radiation exposure. , 1994, Photodermatology, photoimmunology & photomedicine.

[6]  L. Packer,et al.  Effect of age on antioxidants and molecular markers of oxidative damage in murine epidermis and dermis. , 1994, The Journal of investigative dermatology.

[7]  G. Ghanem,et al.  Glutathione depletion increases tyrosinase activity in human melanoma cells. , 1993, The Journal of investigative dermatology.

[8]  M. Yamashita,et al.  Components of Volatile Oil from Plants of Polypodiaceae , 1993 .

[9]  D. Vessey,et al.  Characterization of the oxidative stress initiated in cultured human keratinocytes by treatment with peroxides. , 1992, The Journal of investigative dermatology.

[10]  R. Gange,et al.  Effect of glutathione depletion on sunburn cell formation in the hairless mouse. , 1990, The Journal of investigative dermatology.

[11]  T. Shibamoto,et al.  PRODUCTION OF MALONALDEHYDE FROM SQUALENE, A MAJOR SKIN SURFACE LIPID, DURING UV‐IRRADIATION , 1989, Photochemistry and photobiology.

[12]  O. Pastoris,et al.  Influence of aging and drug treatment on the cerebral glutathione system , 1988, Neurobiology of Aging.

[13]  R. Tyrrell,et al.  CORRELATION BETWEEN ENDOGENOUS GLUTATHIONE CONTENT AND SENSITIVITY OF CULTURED HUMAN SKIN CELLS TO RADIATION AT DEFINED WAVELENGTHS IN THE SOLAR ULTRAVIOLET RANGE , 1988, Photochemistry and photobiology.

[14]  T. Toyo’oka,et al.  Simultaneous determination of thiols and disulfides by high-performance liquid chromatography with fluorescence detection , 1988 .

[15]  L. Wheeler,et al.  DEPLETION OF CUTANEOUS GLUTATHIONE BY ULTRAVIOLET RADIATION * , 1987, Photochemistry and photobiology.

[16]  M. Poot,et al.  Influence of cumene hydroperoxide and 4-hydroxynonenal on the glutathione metabolism during in vitro ageing of human skin fibroblasts. , 1987, European journal of biochemistry.

[17]  L. Wheeler,et al.  Depletion of cutaneous glutathione and the induction of inflammation by 8-methoxypsoralen plus UVA radiation. , 1986, The Journal of investigative dermatology.

[18]  Dean P. Jones,et al.  Exogenous glutathione protects intestinal epithelial cells from oxidative injury. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  E Borenfreund,et al.  Toxicity determined in vitro by morphological alterations and neutral red absorption. , 1985, Toxicology letters.

[20]  Y. Yoshimura,et al.  The possible role of squalene and its peroxide of the sebum in the occurrence of sunburn and protection from the damage caused by U.V. irradiation. , 1984, The Journal of toxicological sciences.

[21]  A. Meister Selective modification of glutathione metabolism. , 1983, Science.

[22]  H. Mukhtar,et al.  Effects of diethyl maleate on aryl hydrocarbon hydroxylase and on 3-methyl-cholanthrene-induced skin tumorigenesis in rats and mice. , 1978, Journal of the National Cancer Institute.

[23]  P. Kanaar Follicular-keratogenic properties of fatty acids in the external ear canal of the rabbit. , 1971, Dermatologica.