Abstract
Background
Diabetes mellitus is characterized by a chronic hyperglycemia and might cause skin
pathologies resulting from an ischemic insult. A variety of mechanisms have been suggested
for the damage provided by ischemia-reperfusion injury (IRI) or for hyperglycemic
conditions. Yet, the association between IRI and hyperglycemia together in skin has
been poorly investigated even thought they are both present in diabetic patients.
Objective
To examine the effect of a dual stress combining IRI and hyperglycemia on human keratinocytes—its
ability to cause oxidative damage and inflammatory response via the enzymes xanthine oxidase (XO) and inducible nitric oxide synthase (iNOS).
Methods
HaCaT cells were used as a model to induce IRI and hyperglycemia. In order to assess
the oxidative damage, total antioxidant scavenging capacity (TSC) and GSH/GSSG ratio
were evaluated. iNOS expression was evaluated and its metabolite nitric oxide was
estimated by measuring nitrite levels. XO activity was assessed by uric acid quantification
and by superoxide radical formation. Inflammatory response was determined through
interleukin-6 secretion.
Results
Our observations demonstrate different responses of the cells exposed to single stress
(IRI) compared to dual stress combining also hyperglycemia. However, cells response
exhibited similarity during reperfusion, by enhancing iNOS expression as well as superoxide
levels. While ischemia led to changes in TSC and redox state, reperfusion restored
them to basal levels. IRI also caused the enhancement of secreted IL-6 and uric acid
levels.
Conclusion
iNOS and XO play a major role in IRI and hyperglycemia. Inhibition of one of these
enzymes may be beneficial to skin cells under these conditions.
Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
May 9,
2009
Received in revised form:
April 26,
2009
Received:
February 22,
2009
Identification
Copyright
© 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
