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

[Display omitted] The 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 slow-releasing (GYY4137) an...

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Published in:	Pharmacological research Vol. 115; pp. 255 - 266
Main Authors:	Rodrigues, L., Ekundi-Valentim, E., Florenzano, J., Cerqueira, A.R.A., Soares, A.G., Schmidt, T.P., Santos, K.T., Teixeira, S.A., Ribela, M.T.C.P., Rodrigues, S.F., de Carvalho, M.H., De Nucci, G., Wood, M., Whiteman, M., Muscará, M.N., Costa, S.K.P.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-01-2017
Subjects:	Animals Glyburide - pharmacology GYY4137 Histamine - metabolism Hydrogen sulfide Hydrogen Sulfide - metabolism Hydrogen Sulfide - pharmacology Inflammation - drug therapy Inflammation - metabolism KATP Channels - metabolism Male Mast Cells - drug effects Mast Cells - metabolism Mice Mice, Inbred BALB C Morpholines - pharmacology Neutrophil influx Organothiophosphorus Compounds - pharmacology Plasma extravasation Protective Agents - pharmacology Pruritus Pruritus - drug therapy Pruritus - metabolism Skin Skin - drug effects Skin - metabolism Hydrogen sulfide GYY4137 Plasma extravasation Skin Pruritus Neutrophil influx
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Summary:	[Display omitted] The 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 slow-releasing (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 (3μg/site) or histamine (1μmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3–100nmol 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 125I-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 increased both Tyrode and C48/80-induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S-releasing donors significantly attenuate C48/80-induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine-mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.
ISSN:	1043-6618 1096-1186
DOI:	10.1016/j.phrs.2016.11.006