P44 Does the slow-releasing hydrogen sulfide donor GYY4137 controls inflammation and pruritogen responses in mouse skin?

A growing body of evidence suggests that hydrogen sulphide (H2S) plays a crucial role in both physiological and pathophysiological process, including heart failure, inflammatory lung and articular diseases, erectile dysfunction, diabetes, among others. Poor diabetes control in women (mean glycosylated hemoglobin level The aim of this study is to determine the effectiveness of the slow H2S-releasing donor GYY4137 in reducing itch behaviour and cutaneous inflammation in mouse dorsal skin. The animal protocols were approved by the local ICB-USP Ethics Committee. In order to produce itching behaviour, male BALB/c mice (25–30 g) were anaesthetised with isoflurano and i.d. injected with histamine (1 μmol site−1) alone or co-injected with GYY4137 (0.3–30 nmol site−1; 0.05 ml). Itching behaviour was estimated by measuring the number of scratching bouts over a 40 min period. In a separate set of experiments, animals were pre-treated (−40 min) with the ATP-sensitive K+ (KATP) channel blocker glibenclamide, and then i.d. injected with histamine and Na2S (3 nmol site−1). In addition, we investigated the presence of mRNA for the enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MST) in the mouse naive skin via qualitative RT-PCR. Data are presented as mean ± SEM and were analyzed by ANOVA followed by the Dunnett test. Values of P The i.d. injection of histamine significantly increased the itching frequency as compared to its vehicle Tyrode. Increasing doses of GYY4137 (1–10 nmol site−1) dose-dependently reduced histamine-induced pruritus but failed to inhibit plasma extravasation evoked by histamine. Suppression of histamine-induced pruritus by the H2S donor was not reversed by glibenclamide. A marked mRNA expression for CBS and 3-MST, but not for CSE, was seen in the mouse naive skin. These findings indicate that low doses of GYY4137 in the skin decrease histamine-induced pruritus without affecting the associated local inflammation. This protective effect does not appear to be mediated by KATP channels activation. Financial support: FAPESP, CAPES and CNPq.