Molecular protection against free radicals

Enhanced free radical generation from internal and external sources causes premature ageing of the skin and accelerates photoageing. The most well-known free radical species are the reactive oxygen species (ROS), which are able to damage biological macromolecules such as DNA, carbohydrates, lipids and proteins.1 Ageing and photoageing are generally associated with impaired antioxidant capacity of tissues, resulting in oxidative stress2 which is a general term used to describe the steady state level of oxidative damage in a cell, tissue, or organ, caused by ROS. Skin is chronically exposed to both endogenous and environmental pro-oxidant agents, being a major target of oxidative stress. Although the skin possesses extremely efficient antioxidant activities, during ageing, ROS levels rise and antioxidant activities decline.

Ageing is associated with changes in the molecular structure of DNA, proteins and lipids. Proteins are known to be important targets for oxidative modifications. Direct oxidation of proteins by ROS yields highly reactive carbonyl derivatives (RCS).2 RCS are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation.3 Intracellular RCS are suggested to play an important role in oxidative stress-related mutagenesis and carcinogenesis through their inhibitory effect on DNA repair mechanisms as well as on induction of DNA damage.4 Trans-4-hydroxy-2-nonenal (4-HNE) is among the most abundant and cytotoxic of the RCS. 4-HNE is a major electrophilic product of lipid peroxidation caused by oxidative stress which is able to bind to various kinds of proteins, and impairs their function. It has been demonstrated that 4-HNE can greatly inhibit DNA repair capacity in human cells through its direct interaction with repair proteins.5 Reactive nitrogen species (RNS) are radical-nitrogen based molecules that can also cause extensive cell damage, which in turn may lead to age-related diseases due to structural alteration of proteins, inhibition of enzymatic activity, and interferences of the regulatory function. Peroxynitrite is one of the most powerful RNS, and exhibits a wide array of tissue damaging effects ranging from lipid peroxidation and DNA damage to inactivation of enzymes via protein oxidation and nitration. Tyrosine nitration is an irreversible process which compromises the cyclic interconversion between the phosphorylated and non-phosphorylated form of tyrosine.6 Skin is constantly challenged by a number of physical and chemical stressors that may impair its function and physiology. Protection response of all organisms is characterised by an increase in the synthesis of evolutionary highly conserved proteins: the Heat Shock Proteins (HSP) or stress proteins. Heat Shock Proteins are believed to represent a mechanism of cellular stress response that protects intracellular proteins from damaging events and subsequent challenges.7 Hsp72 (also named Hsp70) is considered the major Hsp responsible for the protective function in human skin. Under stress conditions, Hsp72 expression is greatly enhanced, and despite being Hsp70 in an inducible form, its role in keratinocytes is so important that it also presents basal expression. However, protection afforded by Hsp72 induction may be impaired with ageing rendering the cell more vulnerable to environmental attacks.8

 Lipotec has designed three revolutionary active ingredients which create an intelligent molecular protection against free radicals and daily-faced common stressors’ harmful effects, thus producing innovative prevention against premature ageing: Preventhelia, Lipochroman-6 and Thermostressine. The molecule Lipochroman-6 (now referred to as Dimethylmethoxy chromanol) is a cosmetic active with a powerful antioxidant activity, thanks to its ROS and RNS scavenging properties. The tetrapeptide Preventhelia (now referred to as Diaminopropionoyl Tripeptide-33) presents a significant photoprotective effect on skin cells, protects cells from UVA-induced DNA damage and is able to promote the DNA repair system capacity. Diaminopropionoyl Tripeptide-33 is also able to quench 4-HNE, therefore inhibiting the formation of carbonylated proteins and preventing DNA damage by protecting the proteins involved in DNA repair. The molecular cosmetic peptide Thermostressine (now referred to as Acetyl Tetrapeptide-22) is a Hsp70 expression booster and is able to confer protection to skin cells from stressors such as UVB radiation, heat, cold and dehydration of skin cells.