Prof. Dr.
Lajos Kemeny
Endocannabionid
containing topical product ameliorates p53 activation and thymine dimers formation
in human skin in vivo
Department of Dermatology, University of Szeged (Hungary)
Endocannabinoids are endogenous ligands of cannabinoid
receptors and are ubiquitously present in nearly all aerobic cells. Research
in the last decade revealed the involvement of endocannabinoids in cognitive
functions, pain perception, appetite and food intake, drug and alcohol dependence,
hormone release, reproduction, immune response, and in gastrointestinal and
cardiovascular function. N-palmitoylethanolamine is the most abundant and the
most studied endocannabinoid, with potent antioxidant and anti-inflammatory
activity. In the present study we investigated the effect of N-palmitoylethanolamine
(formulated as a commercially available creme) on the ultraviolet-B (UVB) induced
thymidine dimer formation and p53 activation in normal human skin. Furthermore,
we compared the anti-inflammatory effects of N-palmitoylethanolamine containing
creme and 1% hydrocortisone actetate containing cream in patients with atopic
dermatitis.
The effects of N-palmitoylethanolamine containing creme on UVB-induced thymidine
dimer formation and p53 expression were studied in 5 healthy volunteers. The
buttocks of the individuals were treated with N-palmitoylethanolamine containing
creme or with the ointment base for one months, than irradiated with 2xMED of
UVB light. Twenty four hours thereafter, the same skin areas were than irradiated
again, and just after irradiation biopsies were taken from both the nonirradiated,
and each irradiated areas. The paraffin embadded tissue specimens were than
stained with anti-human p53-antibodies and anti-thymidine dimer antibodies.
We found that pretreatment of the human skin with N-palmitoylethanolamine containing
creme inhibited the UVB-induced thymidine dimer formation and p53 expression
in the human skin .
Eighteen patients with atopic dermatitis have been enrolled into the comparative
study, where the patients's left side was treated with N-palmitoylethanolamine
containing creme and the right side with hydrocortisone 1% creme. Three patients
were dropped out because of lack of complience. We found that N-palmitoylethanolamine
containing creme and hydrocortisone 1% creme were equally effective in reducing
the itch, skin infiltration, excoriation and lichenification of the atopic dermatitis
lesions. Hydrocortisone 1% creme was significantly better than N-palmitoyletanolamine
containing cream in reducing the erythema of the lesions throughout the 3-week
investigational period (Wilcoxon signed ranks test, p<0.05). On the other
hand, N-palmitoylethanolamine containing creme proved to be significantly better
than hydrocortisone 1% in reducing skin dryness in the first week of the treatment
(Wilcoxon signed ranks test, p<0.05). Patients with mild to moderate atopic
dermatitis responded to N-palmitoylethanolamine containing creme at least as
well as to hydrocortisone 1%, with the exemption in reducing erythema, but the
improvement of skin dryness was significantly better in N-palmitoylethanolamine
containing creme treated side as compared to that of hydrocortisone 1% treated
side.
These results suggest that the N-palmitoylethanolamine containing creme is
highly effective in reducing UVB-induced oxidative damage in human skin, and
is also suppressing the clinical symptoms of patients with atopic dermatitis.
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