Toward Mechanism‐based Antioxidant Interventions

Abstract

It is generally accepted that one of the major and important contributions to skin aging, skin disorders, and skin diseases results from reactive oxygen species. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents, such as ultraviolet light, causing oxidative stress. Accelerated cutaneous UV-induced aging, photo aging, is only one of the harmful effects of continual oxygen radical production in the skin. Interestingly, our ELISA assays of 8-oxo-2'-deoxyguanosine in skin of young and old Balb/c mice showed that cumene hydroperoxide-induced accumulation of the biomarker of oxidative DNA damage in skin of 32-week-old mice occurred independently of their vitamin E status, while no accumulation of oxo8-dG was detectable in the skin of young animals. This suggests that vitamin E is not the major protector of skin against cumene hydroperoxide-induced oxidative stress. Production and accumulation of apoptotic cells is one of the characteristic features of skin damage by oxidative stress that, in the absence of effective scavenging by macrophages, dramatically enhances oxidative damage and inflammatory response. In our model experiments, we demonstrated that Cu-OOH induces significant oxidative stress in phospholipids of normal human epidermal keratinocytes (NHEK) whose characteristic feature is an early and profound oxidation of phosphatidylserine (PS), likely related to PS externalization. Since externalized PS is a signal for recognition of apoptotic cells by macrophage scavenger receptors, PS oxidation may be translatable into elimination of thus damaged NHEKs. Experiments are now underway to determine whether inhibition of PS oxidation by antioxidants may interfere with important signaling functions of oxidative stress in eliminating apoptotic cells.

Low-Molecular-Weight Hydrophilic and Lipophilic Antioxidants in Nonmelanoma Skin Carcinomas and Adjacent Normal-Looking Skin

“…As demonstrated in our data, vitamin E appears to react mostly as enzyme regulator and less as free radical antagonist. Our results are also in accordance with those on superoxide dismutase and Cu,Zn-superoxide dismutase, where a reduction of their activity was found in various cancer tissues compared with normal tissues [24,38,39]. The differences in the behavior of enzymic and nonenzymic antioxidants in the epidermis and dermis were also noticed by other researchers [18,19].…”

“…Therefore, it is assumed that the local accumulation of lipophilic LMWA maybe induces toxicity to skin tissues and that the protective mechanism of the body does not respond under these conditions. Kagan et al [38] demonstrated that in accelerated cutaneous UV-induced aging the production of 8-oxo-2′-deoxyguanosine was independent from the vitamin E status. As demonstrated in our data, vitamin E appears to react mostly as enzyme regulator and less as free radical antagonist.…”

Angiopoietin-1 Reduces H2O2-Induced Increases in Reactive Oxygen Species and Oxidative Damage to Skin Cells

“…Solar radiation increases 8OHDG in the skin and humans receiving indoor tanning UV radiation incur DNA damage (The International Agency for Research on Cancer Working Group on artificial ultraviolet light and skin, 2007). ROS-induced accumulation of 8OHDG DNA damage occurs in skin of old, but not young, mice, indicating a role in photoaging(Kagan et al, 2002). Ang1 protects against nuclear DNA damage,…”

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX)

“…Vitamin E, a known antioxidant, inhibits lipid peroxidation and interferes with the process of cytokine-mediated cytotoxicity by acting as a free oxygen scavenger (12,13). It has also been shown that lipid peroxidation is involved in the cytotoxic effects of cytokines on rat islets and that the inhibition of this process protects islet beta cells from the combined cytotoxic effects of interleukin 1, tumor necrosis factor and interferon gamma (14).…”