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Protein oxidative damage in the stratum corneum: evidence for a link between environmental oxidants and the changing prevalence and nature of atopic dermatitis in Japan

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Abstract:

Summary 

Background The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation.

Objectives To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls.

Patients and methods Carbonyl moieties in skin biopsies from 75 patients with AD were assessed using both spectrophotometric and immunohistochemical detection of the formation of dinitrophenylhydrazone (DNP) from dinitrophenylhydrazine (DNPH). These were compared with diseased and normal controls. Lipid peroxidation was also assessed by staining with antibody to 4-hydroxy-2-nonenal (4-HNE), an aldehyde product of oxidized ω-6-fatty acids. In addition, the activity of superoxide dismutase (SOD), an effective scavenger of ROS, was assessed and compared with controls.

Results The level of protein carbonyl moieties in patients' skin was elevated and correlated directly with the severity of the disease. In contrast, DNP formation was not significantly increased in diseased controls, when compared with healthy volunteers, and no statistical significance was found between the two control groups. SOD activity was increased except for those with extra-severe disease. Positive staining with anti-DNP antibody and anti-4-HNE antibody were found in the most superficial layers of the stratum corneum.

Conclusions This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD.

Keywords: atopic dermatitis; dinitrophenylhydrazone; environmental pollutants; oxidative protein damage; superoxide dismutase activity

Document Type: Research Article

DOI: https://doi.org/10.1046/j.1365-2133.2003.05417.x

Affiliations: Niwa Institute for Immunology and Tosashimizu Hospital, 4-4 Asahimachi, Tosashimizu, Kochi 787-0303, Japan

Publication date: 2003-08-01

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