Glutathione and Sunburn / Skin Damage

Author:  Sophie Van Der Helder

A biological antioxidant is defined as “any substance that, when present at low concentrations, significantly delays or prevents the oxidation of oxidizable substrates” [1]. Oxidizable substrates in the body, such as DNA and proteins, can incur damage by accepting electrons from unstable reactive oxygen species (ROS), which are generated by exogenous and endogenous means. Ultra-violet radiation (UVR) is a type of ionizing radiation that significantly increases ROS formation as its short wavelength and high frequency possesses enough energy to knock electrons out of oxygen molecules. This makes them highly unstable. Everyday UVR exposure often leads to sunburn, and long-term repeated exposure can additionally result in substantial skin and DNA damage that may lead to the development of melanoma and other skin cancers [2].

When the body’s antioxidant defence system becomes overwhelmed due to an influx of ROS, a cascade of oxidative damage can occur. If the DNA or membrane of a cell is irreversibly damaged, it will be marked for programmed cell death (apoptosis). This process releases inflammatory markers such as prostaglandins, which are responsible for inducing the symptoms of sunburn: Vasodilation, swelling and pain [3]. Oxidative damage can accumulate over time if UVR exposure is frequent, accelerating photoaging and consequently increasing the appearance of wrinkles, pigmentation and blotchiness.  The Skin Cancer Foundation states that photoaging is responsible for 90% of visible changes to the skin [4]. The symptoms of photoaging occur due to the oxidation of dermal collagen fibre bundles, which are proteins responsible for providing strength and elasticity to our skin [5]. Since the body produces less collagen as we age, the symptoms of photoaging will naturally accumulate over time. Long-term UVR exposure evidently hastens this process.

Depending on its wavelength, UVR is categorized intoUVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm). Each type differs in their biological activity and ability to penetrate our skin. Of the UVR entering the atmosphere, 90% of UVA, 10% of UVB, and none of the UVC radiation reaches the Earth’s surface. For this reason, the only possible routes of UVC exposure are from man-made devices such as tanning beds and lasers. Radiation in the UVA spectrum is primarily responsible for ROS generation and sunburn, while UVB can directly damage DNA by inducing the formation of thymine-thymine cyclobutane dimers, which can lead to mutation, and potentially skin cancers if not repaired [6]. Considerable levels of OH• (hydroxyl radical) and H₂O₂ (hydrogen peroxide) are produced within 15 minutes of UVR exposure and continue for up to 60 minutes afterwards [2].

Glutathione (GSH) has been shown to play a protective role during UVR exposure via three mechanisms. The primary function of GSH is to neutralize the oxidation capacity of H₂O₂ by converting it to water (see Reaction 1 below). In this process, catalyzed by the enzyme glutathione peroxidase, reduced glutathione (GSH) is oxidized to (GSSG), which the cell then recycles back to the reduced form using the enzyme glutathione reductase (see Reaction 2 below).

Reaction 1. H₂O₂ + 2GSH     —->    2H₂O + GSSG

Reaction 2. GSSG + NADPH + H⁺   —->    2GSH + NADP⁺

Melanin is a skin pigment that acts as a photoprotector by absorbing UVR. The production of melanin in the epidermis (melanogenesis) is accelerated during UVR exposure, which concurrently generates ROS [7]. The second function of GSH is to downregulate UVR-induced melanogenesis, which consequently lowers the increased level of ROS production [7]. Lastly, GSH also supports the activity of DNA repair enzymes [8], lowering the incidence of mutations which are a precursor to skin cancer, as well as apoptosis which leads to sunburn [9].

GSH is only able to protect cells against UVR if there is a sufficient concentration within the cells to address the onslaught of UVR induced ROS.  This can be an issue, as UVA exposure has been shown to deplete GSH in the dermis and epidermis skin tissue [10]. Studies have shown that a diminished GSH pool stimulates apoptosis and leads to increased UVR sensitization and sunburn [11,12]. Research suggests that during UVR exposure, GSH in affected cells is progressively depleted due to inhibition of cysteine transport as well as decreased activity of the enzyme gamma-glutamate cysteine ligase (GCL) [13]. The product of GCL is gamma-glutamylcysteine (GGC), which is an essential precursor to GSH. Taking GGC supplements bypasses the need for GCL to be working at its maximal rate, allowing GSH to be continually produced and hence withstand depletion inside cells.

The risk of cellular oxidative stress can be lowered by limiting exposure to UVR and/or by strategies that increase the cellular GSH pool to provide a buffer against the UVR-induced acute increase in ROS production [10]. During long or acute periods of UVR exposure, the antioxidant defense system will eventually become overwhelmed, as the rate of GSH synthesis is outcompeted by the accumulation of ROS. Supplemental GGC has been shown to increase the intracellular GSH pool [14] and, if consumed before UVR exposure, there is great potential for the skin to further withstand oxidative stress through a heightened GSH antioxidant buffer. Supplements should always be used in conjunction with additional measures such as sunscreen and protective clothing to achieve a decreased risk of sunburn, photoaging and skin cancer.

References

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