Beneficial Effects of Two Hydrogen Sulfide (H₂S)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice

Author(s):Show less -

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 ; Costa, Soraia Katia Pereira ; Spolidorio, Luis Carlos ; Muscara, Marcelo Nicolas

• Document type: Journal article
• Source: PHARMACEUTICS; v. 15, n. 7, p. 19-pg., 2023-07-01.

Abstract

Hydrogen sulfide (H2S) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two H2S-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the H2S-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT. Topical treatment with equimolar doses of either Dex, Dex-TBZ, or Dex-ADT resulted in similar reductions in dermatitis score, scratching behavior, edema, eosinophilia, splenomegaly, and histological changes. In contrast with Dex, the H2S-releasing derivatives prevented IL-4 elevation and oxidative modification of skin proteins. On an equimolar dose basis, Dex-TBZ, but not Dex-ADT, promoted the elevation of endogenous H2S production and GPx activity. Neither Dex-TBZ nor Dex-ADT decreased GR activity or caused hyperglycemia, as observed with Dex treatment. We conclude that the presence of H2S-releasing moieties in the Dex structure does not interfere with the anti-inflammatory effects of this corticosteroid and adds beneficial therapeutical actions to the parent compound. (AU)

• FAPESP's process: 13/04151-3 - Pharmacological evaluation of sulfide hydrogen donors (rapid and slow release) in pruritus and related inflammation in mice skin
• Grantee: Soraia Katia Pereira Costa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/24518-1 - Role of hydrogen sulfide (H2S) in the inflammatory and nociceptive responses induced by carrageenan in the rat temporomandibular joint
• Grantee: Marcelo Nicolas Muscara
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/16409-6 - Effect of hydrogen sulfide (H2S) donors on experimental atopic dermatitis in mice.
• Grantee: Silvia Abigail Coavoy Sanchez
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/14051-2 - Study on the participation and effects of hydrogen sulfide (H2S) on the in vitro vasomotor response of mouse mesenteric artery
• Grantee: Marcelo Nicolas Muscara
• Support Opportunities: Regular Research Grants