The role of free oxygen radicals in the aetiopathogenesis of rosacea
M. O. Öztas, M. Balk*, E. Ögüs, M. Bozkurt, I. H. Ögüs and N. Özer
Experimental Dermatology Original article

Summary
A possible link between superoxide dismutase activity and malondialdehyde level with the clinical manifestations of rosacea was investigated. We found differences in superoxide dismutase activities between mild rosacea (stages I and II) and severe involvement (stage III) groups, as well as between disease and control groups that were statistically significant (P < 0.05). In the mild involvement group (stages I and II), the superoxide dismutase activity was higher than in the control group (P < 0.05), while the malondialdehyde levels did not differ from the control.
In the severe involvement group (stage III), the superoxide dismutase activity was lower than in the control group (P < 0.05), and this was coupled to a raised level of malondialdehyde (P < 0.05). These findings clearly show that in the mild involvement phase of rosacea patients, superoxide dismutase activity was stimulated to protect
the skin against reactive oxygen species so that the malondialdehyde levels were maintained. In contrast, in more severe disease, due to a decrease in the capacity of the antioxidant defence system, the malondialdehyde levels were increased. These findings support the 'antioxidant system defect hypothesis' in rosacea patients.

Clinical & Experimental Dermatology, Volume 28 Issue 2 Page 188 - March 2003

What does all this mean? Marjorie Lazoff, MD, offers this explanation:

Regardless of its pathogenesis, any physical insult, if severe
enough, induces the release of proinflammatory mediators, including
ROIs. This is not unique to rosacea, it is a common pathway for
injury. In fact, some people hypothesize it as THE common pathway
explaining all tissue injury and death, holding the key to perfect
health and theoretical immortality.

For those not familiar, reactive oxygen species (ROS), including
tissue-toxic reactive oxygen intermediates (ROI), are normal
byproducts whenever oxygen is metabolized into water -- a process
which occurs in every cell of the body. ROIs are potentially damaging
to tissues but they are extremely short lived and local enzymes and
metabolic processes usually keep ROIs in check.

However, increased ROIs are generated in times of high metabolic
demands -- illness or other physical stressors, local or systemic
inflammation (as in the presence of neutrophils and other immune
mediators) -- and also specific environmental forces such as sunlight
(to the skin) and smoking and pollution (to the lungs). In these
conditions -- and considering genetic, age, and general health
status -- protective controls may not be adequate. Local damage from
these ROIs occurs, and the damage may even become widespread and
deadly. The pathophysiology involving ROIs is called oxidative
stress.

The damage in oxidative stress includes the lipid-rich cell membranes
where, in the presence of ROIs, lipids are abnormally metabolized.
Cell membranes are very important because they filter chemicals going
in and out of the cell, and because they house receptors that
activate or inhibit cell activities.

This study uses common lab measurements to evaluate oxidative stress
in the skin of rosaceans. Superoxide dismutase (SOD) is one of many
enzymes that destroy ROS, in this case the particular ROS called
superoxide. One of the lipid peroxidation metabolites in plasma and
cell membrane dysfunction is malondialdehyde (MD). SOD and MD are
commonly used to measure oxidative stress in any organ system, or
systemically.

I've noticed through the years that some countries, esp in Eastern
Europe and Japan, are researching free oxygen radicals and oxidative
stress in all diseases, one by one. So taken in context, this is a
banal study documenting what was already known -- in ANY inflammatory
situation, ROIs are formed. The same group has measured SOD and MD in
many other condition -- rosacea is just an example of literally
hundreds of diseases where free radical formation can be shown to
occur. It gets a little silly -- I recall one Japanese study measured
fewer ROSs in children who swam more laps in a pool than other group
of children! <g>

But most research in this area that I'm familiar with over the past
ten years or so is much more serious, and revolves around critical
care -- systemic infections, multiple organ failure, heart attacks
and brain injuries and other situations when low blood flow, and so
decreased oxygen, is occurring. It's truly fascinating stuff but, at
present, has unfortunately not yielded many clinical therapies.

The article reposted by Matija on rosacea-support about the anti-
oxidant properties of topical metronidazole (Metros, Noritate)
provides clinical perspective supporting the same view this article
does: that rosacea is primarily an inflammatory condition with
secondary vascular effects. I don't necessarily agree or disagree but
I see it as increasing important theory in understanding rosacea, esp
recently over the past five years.

For the full context, see Millikan's Proposed Inflammatory
Pathophysiology of Rosacea article:
http://groups.yahoo.com/group/rosacea-knowledge/message/1447

source > http://groups.yahoo.com/group/rosacea-knowledge/message/1466