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Antioxidants explained: Eukarion-134

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#1 Eva Victoria

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Posted 13 February 2008 - 09:08 PM

Free Radicals: Oxygen has been known since the 18th century to be poisonous. The toxicity of oxygen is due to its partially reduced forms called free radicals or Reactive Oxygen Species (ROS). ROS play a key role in all aging theories. The first who spoke about the relation of ROS and aging was Dr Denham Harman (Nobel 1995), in November 1954. The biology of ROS, a relatively new branch, studies the interaction between living matter and ROS.

A free radical is a molecule, atom or molecular fragment, which contains an unpaired electron in its outer orbital shell. All free radicals are extremely reactive and seek out to acquire an electron in any possible way. In the process of acquiring an electron, the free radicals attach themselves to other molecules thereby modifying them biochemically. However, as free radicals steal an electron from other molecules, they convert them into free radicals and breakdown or alter their chemical structure. Normally, ROS are produced by mitochondria and they are byproducts of cell metabolism. ROS are also generated by external factors, such as smoking and UVR. The most important ROS are:

a) superoxide anion (O2)

b) hydrogen peroxide (H2O2)

c) hydroxyl radical (OH). The most dangerous and reactive among them is (OH).

The formation is based on the following reactions:

a) Fenton reaction (1894)

b) Haber Weiss reaction (1934)

Obviously, the key factor in both reactions is H2O2.

The ROS are damaging the cell membranes. This induces the release of pro-inflammatory mediators that will ultimately lead to the activation of MMPs, capable of gradually degrading the ECM. The final result will be the loss of integrity, firmness and elasticity of the skin.

Furthermore, ROS are damaging proteins and DNA, leading to direct cellular damage and, eventually, carcinogenesis. To protect against damage from ROS caused during the normal course of cellular function, biological systems have evolved antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and GSH peroxidase. The SOD blocks O2 and forms H2O2. In turn, H2O2 is degraded by CAT, thus preventing the formation of OH.

In both chronological aging and photoaging, cells produce excessive amounts of free radicals. Additionally, in aging skin and in skin exposed to UVR, naturally occurring antioxidants are in short supply. From this point of view, topical application of antioxidants has been recently suggested as a preventive therapy for skin photoaging and UV-induced cancer.

Description: EUK-134 is a novel, synthetic, low-molecular weight, water-soluble, cell-permeable, salen-manganese complex that exhibits the catalytic actions of both SOD and CAT. Thus, EUK-134 removes O2 and H2O2 and, hence, protects the cells, ECM and DNA against injury caused by the ROS including (EUK-134 catalytically eliminates H2O2 and stops the Haber-Weiss and Fenton reactions. This results in the inhibition of OH formation). Compared with proteinaceous antioxidant enzymes, EUK-134 has a better stability and bioavailability, whereas its activity is not affected by UVR. (It could be interesting to add here the self-regenerating feature of EUK-134 since this is to me a differentiating point).

One of the main characteristics that distinguishes EUK-134 from other anti-oxidants is its capability of regenerating itself during the free radical scavenging procycles. This exceptional property relies in the molecular organization of the molecule itself. Indeed, in a way similar to endogenous SOD, EUK-134 has a Mn (manganese) atom as the active catalytic site.

During the interaction with ROS, the Mn atom undergoes several redox cycles before returning to its original valence state Mn(III) and being ready for another anti-oxidant reaction. In this way, the efficacy of EUK-134 will not rapidly vanish as it is often the case with other anti-oxidants.

General: In vitro and in vivo studies have shown that EUK-134 prevents UVR-induced DNA damage, ROS-associated tissue injury and lipid peroxidation. Thus, it can protect the skin against the ROS-dependent deleterious effects of chronic UVR exposure: photoaging and photocarcinogenesis.

Efficacy Tests / Clinical Trials: Unlike many cosmeceutical ingredients, there is a great deal of research supporting the use and the efficacy of EUK-134 as a protective agent against ROS-associated tissue injury:

According to an in vitro trial, EUK-134 protects primary human keratinocytes against oxidative stress and increases cell survival after UVB irradiation.

In an in vitro study, EUK-134 provided about 50 to 70% protection against various parameters of cell damage and markers of oxidative stress.

In an open label, in vivo, clinical trial, EUK-134 reduced the formation of peroxide lipids after UVA exposure.

In an in vivo clinical trial, EUK-134 reduced the UVB-induced erythema by 46%.

(The only commercially available products are Estee Lauder: DayWear Plus Lotion SPF15 and Clinique: Continous Resque AntiOxidant Moisturizer (for 3 diff. skin types). Estee Lauder Companies have interests in the Boston based firm (EUKARION) who developed this cathalitique antioxidant fo medical use (Parkinson and Alzerheimer disese).

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