Because skin acts as a barrier between the internal and external environment, it is key in the maintenance of homeostasis. It is in continuous communication with the immune, neural, and endocrine systems and therefore, it shares numerous mediators with the central nervous and endocrine systems. The skin of mammals contains all the molecular and biochemical machinery required to synthesise melatonin from tryptophan. The melatonin produced by skin is metabolised, giving rise to different catabolites such as N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). In turn, UVB stimulates the formation of N1-acetyl-5-methoxykynuramine (AMK) from AFMK. These metabolites are more powerful antioxidants than melatonin itself. In the skin, one of melatonin’s most important roles is to counteract the daily oxidative damage induced by UVR and other environmental pollutants. Melatonin acts as an antiapoptotic agent, increasing the viability of cells irradiated with UVR and suppressing the formation of ROS. It also inhibits lipid peroxidation and NO formation, reduces the production of polyamines, and stimulates antioxidant enzymes, as already discussed above. Melatonin stabilises mitochondria by increasing the activity of respiratory complexes and mitochondrial efficiency. All of this reflects the extraordinary properties of melatonin and its potential role in skin care.
It has recently been shown that melatonin regulates the expression of apoptosis-related genes in keratinocytes irradiated with UVR, resulting in an increase in the survival of those cells. The damage produced by ionising radiation is caused by both direct and indirect mechanisms. The direct effects are the result of the disruption of intracellular molecules, while the indirect effects (accounting for approximately 70% of the damage) are because water molecules give rise to the formation of free radicals such as hydroxyl.
It has been shown that melatonin protects cells against the toxic effects of ionising radiation. All of melatonin’s activity in the skin may be the result of its metabolites because UVR stimulates melatonin metabolism, generating AFMK and AMK. Therefore, melatonin can protect the skin’s integrity, helping to maintain the functions of the epidermal barrier, and its antioxidant effects could help to protect keratinocytes and fibroblasts from the damage caused by UVB radiation. Melatonin prevents the erythema and skin damage induced by radiation, as well as having antimutagenic, anticarcinogenic, and oncostatic effects on the skin. Another example of melatonin’s protective effect is a reduction in the damage caused to skin by X-rays. In this sense, the administration of melatonin in combination with radiotherapy is very effective during the treatment of human cancers. Also of note is that pinealectomy in rats is associated with a reduction in skin thickness, producing atrophy of the epidermis, dermis, and hair follicles, while the administration of melatonin reverses these effects. Furthermore, melatonin reduces cutaneous vascular permeability and stimulates angiogenesis, indicating that regular application of melatonin could reduce the development of ulcers and accelerate their healing. Melatonin also inhibits the transcription of α-estrogenic receptor and immunoreactive protein genes in the skin, causing desensitisation of the skin to estrogenic stimuli. All these data indicate that melatonin is an important regulator of the various structures and functions of the skin.