Role of vitamin E in the antioxidant defense system of skin in young and old mice exposure to cumene hydroperoxide.
Murray-AR; Kisin-E; Kawai-K; Kagan-VE; Kommineni-C; Castranova-V; Shvedova-AA
Toxicologist 2005 Mar; 84(Suppl 1):448
The skin is exposed to numerous environmental, chemical, and physical stressors (UV-irradiation) whose injurious action is often associated with the development of oxidative stress. While the skin possesses an elaborate antioxidant (AO) defense system to prevent oxidative stress, excessive exposure to occupational and environmental insults can overwhelm the cutaneous AO capacity. Age-related decline of AO protection may further enhance sensitivity of skin to chemically induced oxidative damage. To evaluate whether aging affected the AO capabilities of the skin, we studied changes in vitamin E, glutathione (GSH), ascorbate, and total AO reserve levels in the skin of female mice from 4 to 32 weeks of age. Among studied AO, we observed the most significant and rapid reduction occurred in the vitamin E content. To study how topical exposure to cumene hydroperoxide (Cum-OOH) affected the AO status of the skin of young/old mice, two models were used: 1) mice given a diet deficient in vitamin E and 2) mice with a genetic deletion of the tocopherol transporter protein (Ttpa knockout). We found that oxidative DNA damage (8-oxo-2'-deoxyguanosine) in skin of old mice (32 weeks) occurred independently of vitamin E status while DNA damage in skin of young animals (13 weeks) exposed to Cum-OOH was dependent upon vitamin E. Cum-OOH induced oxidative stress in old mice as assessed by depletion of GSH, ascorbate, and total AO reserve. Cum-OOH induced morphological changes to a greater extent in the skin of old vitamin E deficient animals compared to young mice. Similar results were found in the Ttpa knockout mice exposed to Cum-OOH; however, the mice only had a 40% reduction in their vitamin E levels and the resulting changes were not as profound as in the mice given the vitamin E deficient diet. In conclusion, AO, in particular vitamin E, play a prominent role in the protection of skin against oxidative injury induced by Cum-OOH exposure in vivo.
Vitamins; Antioxidants; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Skin-exposure; Environmental-exposure; Occupational-exposure; Environmental-stress; Skin-sensitivity; Skin-protection; In-vivo-studies
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana