Supervisors info:
Αγγελική Κουρουνάκη, Αναπληρώτρια Καθηγήτρια, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Μιχαήλ Ράλλης, Επίκουρος Καθηγητής, Τμήμα Φαρμακυτικής, ΕΚΠΑ
Summary:
Skin inflammation is associated with almost all cutaneous disorders. Diabetes mellitus also influences skin physiology producing dryness and accelerating ageing. The development of effective and safe topical anti-inflammatory/antioxidant agents may be beneficial in such cases. The present study was conducted in order to evaluate the effect of a novel multifunctional derivative (AK1) that combines structural moieties of tolfenamic acid (a known NSAID) and cysteine ethyl ester (a known antioxidant molecule).
The study was divided into three parts (studies), firstly in order to estimate the dose which produces the best therapeutic effect and subsequently to study the effect of the selected dose on diabetic skin. In the first study, 5 groups of 8 male hairless SKH-2 mice in each group were exposed to acute UVR (2,5) MED and a (twice) daily topical application of tolfenamic acid 5% (Tolf group) or cysteine ethyl ester (Cys group) (both as reference agents) and AK1 5% (AK1 group) in a mixture of polyethylenoglycols (PEG100/PEG400, 3:1) used as excipient. Additionally, there was another group treated with the Excipient (Excipient group) and one without any treatment (Control). In the second study, 8 groups of 6 male hairless SKH-2 mice were irradiated under the same conditions, while we investigated the topical effect of the above agents, in a dose of 1% and 0.1%, respectively (Tolf 1%, Tolf 0.1% Cys 1%, Cys 0.1%, AK1 1%, AK1 0.1%, Excipient, Control). Finally, a third study was performed in order to examine the pharmacological effect of AK1 1% or reference molecules on irradiated diabetic mice (Τolf, Cys, AK1, Excipient, Control) after diabetes was induced by intraperitoneal administration of STZ (40mg/kg/day, for 5 days).
The parameters that examined were TEWL (transepidermal water loss), Stratum Corneum (SC) Hydration, Thickness and Elasticity. We also measured the concentration of endogenous antioxidants (glutathione, ascorbic acid and uric acid) using HPLC. Finally, histopathological studies took place on skin sections of the irradiated dorsal skin of the mice using Hematoxylin and Eosin staining.
The results were promising considering the amelioration of the inflammation in AK1-treated groups, as well as the reinforcement of antioxidant defense system in the skin. In conclusion, the outcome suggests that the novel derivative of NSAID with cysteine ethyl ester (AK1) may exhibit an effective therapeutic effect in UVB-induced inflammatory and oxidative skin damages in conditions such as diabetes mellitus.
Keywords:
inflammation, skin, antioxidant, anti-inflammatory, diabetes
