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Effect of hydrogen sulfide (H2S) donors on experimental atopic dermatitis in mice.

Grant number: 17/16409-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2017
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Marcelo Nicolas Muscara
Grantee:Silvia Abigail Coavoy Sanchez
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by eczematous lesions associated with severe pruritus and immunoglobulin E (IgE) overproduction that affects children and adults with a high prevalence. Even though some patients respond satisfactorily to topical treatments, this type of therapies are not always effective, and systemic treatments are often necessary, despite the frequent side effects, especially when used for long periods of time. Therefore, the development of effective and safe therapies for AD is a need. Previous studies from our laboratory show that hydrogen sulfide (H2S) donors can reduce inflammation and pruritus secondary to the activation of either histaminergic or non-histaminergic pathways in the mouse skin. However, the therapeutic potential of H2S as an alternative treatment of AD signs and symptoms has not yet been studied. Thus, the present project aims to investigate the effects of the administration of different H2S donors (H2S-releasing steroidal anti-inflammatory and mitochondria-targeting donor compounds) on AD induced in mice by the epicutaneous application of the allergen (hapten) 2,4-dinitrochlorobenzene. The study will include: 1) evaluation of skin dermatitis severity and analysis of scratching behavior, 2) quantification of endogenous H2S production, and protein and gene expression of the H2S-producing enzymes (CSE, CBS and 3MST) as well as filaggrin in the skin, 3) measurement of IgE as well as the circulating cytokines IL-4, IL-5, IL-13, IFN-³ and TSLP, 4) histopathological analysis of the skin, and 5) analysis of oxidative stress markers and antioxidant enzymes in the skin. Considering H2S as a promising therapeutic agent, it is expected that this study will contribute to define the potential and limitations of H2S-based compounds for the control of signs and symptoms of AD.

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COAVOY-SANCHEZ, SILVIA A.; COSTA, SORAIA K. P.; MUSCARA, MARCELO N.. Hydrogen sulfide and dermatological diseases. British Journal of Pharmacology, v. 177, n. 4, SI, p. 857-865, . (17/16409-6, 14/24518-1, 16/06146-5)
COAVOY-SANCHEZ, SILVIA ABIGAIL; SANTAGADA, VINCENZO; CALIENDO, GIUSEPPE; COSTA, SORAIA KATIA; SEVERINO, BEATRICE; MUSCARA, MARCELO NICOLAS. A hydrogen sulfide-releasing dexamethasone derivative attenuates atopic dermatitis severity signs and the associated oxidative stress markers in mice. British Journal of Pharmacology, v. 177, n. 11, p. 2-pg., . (17/16409-6)
COAVOY-SANCHEZ, SILVIA ABIGAIL; CERQUEIRA, ANDERSON ROMERIO AZEVEDO; TEIXEIRA, SIMONE APARECIDA; SANTAGADA, VINCENZO; ANDREOZZI, GIORGIA; CORVINO, ANGELA; SCOGNAMIGLIO, ANTONIA; SPARACO, ROSA; CALIENDO, GIUSEPPE; SEVERINO, BEATRICE; et al. Beneficial Effects of Two Hydrogen Sulfide (H2S)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice. PHARMACEUTICS, v. 15, n. 7, p. 19-pg., . (13/04151-3, 14/24518-1, 17/16409-6, 19/14051-2)
COAVOY-SANCHEZ, SILVIA ABIGAIL; MARQUES, LEONARDO ANDRE DA COSTA; COSTA, SORAIA KATIA PEREIRA; MUSCARA, MARCELO NICOLAS. Role of Gasotransmitters in Inflammatory Edema. Antioxidants & Redox Signaling, v. N/A, p. 20-pg., . (13/04151-3, 14/24518-1, 17/16409-6, 19/14051-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANCHEZ, Silvia Abigail Coavoy. Effect of hydrogen sulfide (H2S) donors on experimental atopic dermatitis induced in mice.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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