Pharmacological evaluation of a microemulsion containing an slow release donor of H2S (GYY4137) in an experimental model of psoriasis

Abstract

Psoriasis is a chronic inflammatory disease, immune-mediated, with 2-4% of global incidence. Characterized mainly by skin lesions associated with intense itching, which greatly reduces the life quality of patients. Neither the classic anti-inflammatory steroid therapy nor biological agents is always effective, besides the high cost and serious adverse effects, as well as works efficiently the H1 antihistaminic therapy. Thus, the search for alternative or complementary treatments to alleviate the symptoms and signs (eg, pruritus, desquamation) of this disease is needed. Previous findings from this group showed, for the first time, that the intradermal injection (i.d.) of fast and slow release donors of hydrogen sulfide (H2S) reduced skin inflammation and itching evoked by histamine or the mast cell desgranulator agent compound 48/80. However, the therapeutic potential of these donors on chronic itching and other related symptoms associated with psoriasis has not yet been established. In this study, we aim to: i) evaluate and pharmacologically characterize the protective effect of a topical microemulsion containing an slow release donor of H2S (GYY4137) on psoriasis induced by imiquimod cream in BALB/c mice; ii) to investigate the possible involvement of novel cytokines (IL-36 and IL-31) and neuropeptides (CGRP and substance P) in the mechanism of itching and inflammation in this model; iii) to establish the possible interrelationship of IL-31 with transient potential vanilloid receptor (TRPV1), via an increase in [Ca2 +], via culture of neurons from the dorsal root ganglion. Knowing the anti-inflammatory and anti-pruritus potential of H2S donors in acute inflammation, it is expected that this study contribute to defining new therapeutic strategies in the control of chronic pruritus and other signs and symptoms related to psoriasis. (AU)