How Metrogel Works Part 2 – Free Oxygen Radicals

Written by on September 4, 2007 in Metrogel 1%, What Causes Rosacea? with 0 Comments

Another recently published paper that seeks to understand the role of Reactive Oxygen Species in the development of rosacea. The inflammatory pathway that leads to rosacea symptoms is slowly gaining more and more attention.

All rosacea sufferers should do themselves a favor and do some reading on the role of inflammation in rosacea. This is the most exciting direction for rosacea research, in my opinion. Though it can feel like you are reading a foreign language, I’d encourage everyone to stick at it.

More links at the bottom, but 2 places to start: Examining Inflammation as a Common Factor in Theories of Rosacea Pathophysiology (via Collagenex’s RosaceaToday info site) and Role of Inflammation (put together by Dan in the RSRP).

Even though there is a bit of a love hate relationship with the metronidazole based rosacea treatments, examining how it works is leading to some new and useful research.

Properties of metronidazole on free oxygen radicals in a skin lipid model system.

J Pharm Pharmacol. 2007 Aug; 59(8):1125-30, Authors: Narayanan S, Hunerbein A, Getie M, Jackel A, Neubert RH

Reactive oxygen species (ROS) play a vital role in the pathophysiology of the skin disease rosacea, a chronic, genetically-determined and UV-triggered disease, leading to facial redness and blemishes and exhibiting a deep impact on a patient’s self-esteem and quality of life. ROS can cause oxidative damage to nucleic acids, sugars, proteins and lipids, thereby contributing to adverse effects on the skin.

Metronidazole has been the first-line topical agent therapy for many years; nevertheless the mechanism of action is still not well understood. The therapeutic efficacy of metronidazole has been attributed to its antioxidant effects, which can involve two pathways: decreased generation of ROS within tissues or scavenging and inactivation of existing ROS. Previous investigations have shown that metronidazole reduces ROS by decreasing ROS production in cellular in-vitro systems. The aim of the following study was to demonstrate that metronidazole additionally exhibits antioxidative properties in a cell-free system, by acting as an antioxidant scavenger.

A simple skin lipid model (oxidative) system and a complex skin adapted lipid system in conjunction with thiobarbituric acid (TBA) test, a quantitative assay for the detection of malondialdehyde (MDA) and therefore lipid peroxidation, were used to determine the antioxidative properties of metronidazole after UV irradiation. Results clearly show that metronidazole has antioxidative properties in a cell-free environment, acting as a free radical scavenger. Simple skin lipid model: in the presence of 10, 100 and 500 mug mL(-1)metronidazole the MDA concentration was reduced by 25, 36 and 49%, respectively. Complex skin lipid system: in the presence of 100 and 500 mug mL(-1)metronidazole the MDA concentration was reduced by 19 and 34%, respectively.

The results obtained in this study and from previous publications strongly suggest that metronidazole exhibits antioxidative effects via two mechanisms: decrease in ROS production through modulation of neutrophil activity and decrease in ROS concentration by exhibiting ROS scavenging properties. The remarkable clinical efficacy of metronidazole in the treatment of rosacea is probably due to its ability to decrease ROS via different mechanisms, thereby protecting skin components from induced damage.

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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