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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