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Reilly et al. Plast Aesthet Res 2021;8:2 I http://dx.doi.org/10.20517/2347-9264.2020.153 Page 13 of 24

Figure 9. Free radical damage occurs when unpaired electrons attack the electrons in the outer shell of a nearby atom. Antioxidants
protect the cellular constituents by donating an electron to neutralize the free radical species, after which they can be recycled, repaired,
regenerated, or removed. (By permission of MINERVA Research Labs Ltd - London)

efficient for the cell to recycle, repair or regenerate small molecular weight species such as ascorbic acid
and this effectively keep larger molecular weight structures such as protein, lipids and DNA protected from
damage [Figure 9].

Ascorbic acid is capable of interacting with a range of free radical species to facilitate their detoxification.
In the process the ascorbic acid itself is converted into a stable ascorbyl free radical, which is a much less
reactive species and therefore less likely to cause oxidative damage to cellular components. The ascorbic
acid can be recycled via cytosolic glutathione-dependent pathways or membrane-bound NADH-dependent
[78]
reductase pathways . Vitamin C also is able to preserve the activity of vitamin E by converting the
[79]
tocopheryl radical back to its native form, restoring the biological activity of the tocopoherol species .

It is important to realise that ROS threat to collagen integrity and content in the ECM can be generated
through many distinct pathways. In addition to UV-radiation, other mechanisms include generation
of Advanced Glycation End products (AGE), Advanced Lipid oxidation End products (ALE), diet and
lifestyle, alcohol consumption, smoking or pollution related xenobiotic metabolism which can be associated
[70]
with production of polycyclic aromatic hydrocarbon species .

Within the collagen protein backbone, early glycation reactions can occur in which glucose reacts in a non-
enzymatic and reversible manner with free amino groups of lysine. Although this reaction is reversible,