Complementary Antioxidant Function of Caffeine and Green Tea Polyphenols in Normal Human Skin Fibroblasts
July 2011 | Volume 10 | Issue 7 | Original Article | 753 | Copyright © 2011
Jared Jagdeo MD MS and Neil Brody MD PhD
SUNY Downstate Medical Center, Department of Dermatology, Brooklyn, NY
The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of these oxidants´ ability to induce DNA mutations and produce lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (HNE). Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals and HNE. The purpose of this research is to investigate the ability of antioxidants green tea polyphenols (GTPs) and caffeine, alone and in combination, to modulate the hydrogen peroxide (H2O2)-induced upregulation of reactive oxygen species (ROS) free radicals and HNE in normal human skin fibroblast WS-1 cells in vitro. GTPs and caffeine were selected for evaluation because these compounds have demonstrated antioxidative properties in various skin models. Furthermore, GTPs and caffeine share a close natural botanical association as caffeine is present in green tea, as well. Hydrogen peroxide is a well-known generator of free radicals that is produced during endogenous and UV-induced oxidation processes in human skin and was used to upregulate ROS and HNE in normal human fibroblast WS-1 cells. Using a flow cytometry-based assay, the results demonstrate that at 0.001% concentration, green tea polyphenols alone, and in combination with 0.1 mM caffeine, inhibited the upregulation of H2O2-generated free radicals and HNE in human skin fibroblasts in vitro. Caffeine alone demonstrated limited anti-oxidant properties.
J Drugs Dermatol. 2011;10(7):753-761.
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The number of skin cancers continues to rise, and account for approximately 40 percent of all cancers reported in the United States, resulting yearly in numerous skin surgeries and approximately 9,500 deaths.9,14,30 A variety of studies have demonstrated that repeated and intense exposures to solar ultraviolet light (UV) contribute decisively to human skin carcinogenesis.3,9,30 UV radiation is known to generate hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) free radicals, which frequently damage DNA, RNA, lipids and proteins in human skin.2,9,10,13,18,22,30,32,38,43,48,51
The evidence available suggests that the generation of ROS and lipid peroxidation products is an important mechanism responsible for changes observed during human skin aging and carcinogenesis.16,56 In addition to the exogenous generation of ROS by environmental (pollution, smoking, UV) and other factors, ROS are also byproducts of endogenous mechanisms that include normal metabolic processes, such as mitochondria- based p450 cycling, that are linked to intrinsic aging.4 ROS -induced oxidative damage to cells is often compounded over time and may be increased or reduced by a variety of factors including cellular metabolism and repair, environmental, hormonal, nutritional and toxicological contributions.31
ROS-induced oxidative damage of cellular membrane fatty acids is a process termed lipid peroxidation. Lipid peroxidation results in the generation of byproducts such as 4-hydroxy- 2-nonenal (HNE), a highly reactive second messenger aldehyde, that is released intracellularly and extracellularly.34,53 HNE is important to study because of the likely role HNE has in human skin aging and carcinogenesis. HNE forms adducts with DNA and proteins, resulting in genotoxic and neutrophil chemotactic effects, suggesting that HNE plays an important role in human skin aging, inflammation and carcinogenesis.8,17,24,53 When applied topically to CD1 mice, HNE followed by tumor promoter tissue plasminogen activator (TPA) induced skin tumors.7 Furthermore, the detection of increased HNE protein adducts in areas of actinic elastosis in sun-damaged human skin suggests that HNE may play a role in the mutagenic activity that occurs during UV-induced damage and should be carefully studied in human skin carcinogenesis.51