Hydrogen peroxide & skin ageing

SPC January 2008

Hydrogen peroxide (H2O2) was first isolated in 1818 by Louis Jacqueous Thenard by reacting barium peroxide with nitric acid. It is a pale blue liquid which appears colourless in a dilute solution. It is a weak acid and has a strong oxidising property and is therefore a powerful bleaching agent. It is one of the most power-ful oxidisers known and is stronger than chlorine, chlorine dioxide and potassium permanganate. It is used in a number of products, including hair dyes, and it is a component of some tooth whitening products.

What does H2O2 have to do with ageing?

Well, it has a major role to play in chronological as well as in photoageing. Hydrogen peroxide plays a pivotal role because it is generated from nearly all sources of oxidative stress and oxygen radicals. Mitochondria are the major sources of production of hydrogen peroxide. Mitochondria are sometimes described as cellular powerhouses because they generate most of the cell’s supply of adenosine triphosphate (ATP), used as a source of chemical energy. The reactive oxygen species that are generated by mitochondrial respiration, including hydrogen peroxide, are potent inducers of oxidative damage and mediators of ageing. It is not clear, however, whether oxidative stress is the result of a genetic programme or the byproduct of physiological processes. Recent findings demonstrate that a fraction of mitochondrial H2O2, produced by a specialised enzyme as a signalling molecule in the pathway of apoptosis, induces intracellular oxidative stress and accelerates ageing. It is quite conceivable to assume that the genes that control H2O2 production are selected determinants of lifespan.

So how does hydrogen peroxide cause chronological ageing?

Hydrogen peroxide and superoxide anion (O2+) are normal metabolites in aerobic cells. For example, H2O2 is formed from O2+ in the presence of superoxide dismutase (SOD) and then converted to H2O and O2 by the enzymes catalase or glutathione peroxidase. Glucose oxidase produces H2O2 directly whereas xanthine oxidase produces O2+, which then gets converted to H2O2 by SOD, which can react with free iron or copper to form the hydroxyl radical (HO). In addition to these toxic electron transport chain reactions of the inner mitochondrial membrane, the mitochondrial outer membrane enzyme monoamine oxidase catalyses the oxidative deamination of biogenic amines resulting in a large production of H2O2 that contributes to an increase in the steady state concentrations of reactive oxygen species within both the mitochondrial matrix and cytosol. Reactive oxygen species generated by mitochondria, or from other sites in or outside the cell, cause damage to mitochondrial components and initiate degradation.

And photoageing?

H2O2 can be increased in inflammatory states and can also be formed by exposure to radiation. It has also been shown that light driven formation of hydrogen peroxide is responsible for advanced glycation end products (AGE) phototoxicity, supporting the general hypothesis that extracellular matrix (ECM)-bound chromophores are endogenous sensitisers of UV phototoxicity in human skin. Hydrogen peroxide is able to cross cell membranes easily and, in conjunction with Fe2+, generates highly toxic hydroxyl radical. Both singlet oxygen and hydroxyl radical can initiate lipid peroxidation. It has been shown that H2O2 can induce cell death in normal human keratinocytes.

Both prokaryotic and eukaryotic cells have inducible and adaptive defences to counter oxidative damage. To counteract the harmful effects of reactive oxygen species (ROS), the skin is equipped with antioxidant defence systems consisting of a variety of low molecular weight antioxidants (eg vitamins C and E) and antioxidant defence enzymes (eg superoxide dismutase, glutathione peroxidase, catalase) forming an antioxidant network. The antioxidant network is responsible for maintaining the equilibrium between pro-oxidants and antioxidants. However, the antioxidant defence can be overwhelmed by increased exposure to exogenous sources of ROS.

The molecular mechanisms by which hydrogen peroxide is sensed and the increasing evidence that antioxidant enzymes play multiple, key roles as sensors and regulators of signal transduction in response to hydrogen peroxide. Hydrogen peroxide has been shown to act as a second messenger mediating intracellular redox-sensitive signal transduction. Hydrogen peroxide is also able to transmit pro-inflammatory signals from one cell to the other and this action can be inhibited by endogenous produced glutathione peroxidase or catalase. Signalling functions of superoxide and hydrogen peroxide in enzymatic phosphorylation/dephosphorylation reactions are now well documented. Hydrogen peroxide signalling in the dephosphorylation reactions by protein phosphatases and in the activation of protein kinases is actually mediated by superoxide formed during the conversion of H2O2 into superoxide by the oxidised superoxide dismutase. There are at least three options for skin protection:

1. Quenching superoxide anion radicals: A wide variety of polyphenolics are very effective superoxide anion quenchers. For example, standardised extracts of green tea, Phyllanthus emblica (Emblica) etc or well-defined natural polyphenolics like epigallo catechin 3-gallate.

2. Inhibiting the activity of glucose oxidase or monoamine oxidase enzymes: For example, resveratrol is an efficient inhibitor of glucose oxidase. It is wise to stay away from monoamine oxidase inhibitors for skin protection purposes as they are used as anti-depressants.

3. Converting hydrogen peroxide to water and oxygen: This can be achieved by inducing synthesis of glutathione peroxidase or catalase. For example, hexylresorcinol (Synovea HR) and resveratrol are very effective stimulators of glutathione peoxidase whereas Emblica is a good stimulator for catalase.

Topical formulations using compounds capable of reducing hydrogen peroxide-induced skin damage are likely to lead to further improvements in the way we protect our skin from overexposure to the sun.