Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

Abstract

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.Pharmacological Research http://dx.doi.org/10. 1016/j.phrs.2016.11.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Graphical abstract RESEARCH PAPER ABSTRACTThe recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slowreleasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR)were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.)injected with C48/80 (3 µg/site) or histamine (1 µmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3 -100 nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125 I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis exacerbated C48/80-induced responses, whereas the blockade of KATP channels by glibenclamide did not. Highperformance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) revealed that Na2S and LR, but not GYY4137, significantly attenuated C48/80-induced histamine release from rat peritoneal mast cell in vitro. We provide first evidences that H2S exerted protective effect against acute pruritus mediated via histaminergic pathways in murine skin, thus making of H2S donors a potential alternative/complementary therapy for treatment of acute pruritus.

Sulphurous Mineral Waters: New Applications for Health

“…Sulphurous mineral water exerts beneficial anti-inflammatory, keratoplastic, and antipruritic effects [49]. Its bactericidal and antifungal properties have determined its use for the treatment of infected leg ulcers, tinea versicolor, tinea corporis, and tinea capitis [50].…”

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

“…Nowadays, more and more studies have focused on the role of H 2 S in the skin. One group found that H 2 S might be a potential agent for allergic skin diseases and related pruritus . Clinical and experimental data indicated that H 2 S‐related pathway was involved in melanoma .…”

Hydrogen sulfide and dermatological diseases

“…The study fromShimizu et al (2013) showed that in mice with the cutaneous Arthus reaction, the exogenous application of NaHS resulted in attenuated inflammatory reaction, TNF-α and IFN-γ expression, and reduced number of neutrophils recruited to the skin lesions.H 2 S also plays an important role on the pruritogenic response. We have previously shown that inhibition of endogenous H 2 S synthesis with β-cyano-L-alanine (a CSE/CBS inhibitor) results in significant potentiation of the scratching behavior induced by compound BJP 48/80 in mice, along with increased neutrophil recruitment, as measured by myeloperoxidase activity(Rodrigues et al, 2017). Moreover, H 2 S donors can have important therapeutic applications for treatment of both histaminergic and non-histaminergic pruritus in mice(Coavoy-Sánchez et al, 2016;Rodrigues et al, 2017).…”