Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Carvacryl acetate, a novel semisynthetic monoterpene ester, binds to the TRPA1 receptor and is effective in attenuating irinotecan-induced intestinal mucositis in mice

2017; Oxford University Press; Volume: 69; Issue: 12 Linguagem: Inglês

10.1111/jphp.12818

2042-7158

Elenice Monte Alvarenga, Nayara Alves de Sousa, Simone de Araújo, José Lopes Pereira Júnior, Alyne Rodrigues de Araújo, Bruno Iles, Dvison M. Pacífico, Gerly Anne de Castro Brito, Emmanuel Prata de Souza, Damião Pergentino de Sousa, Jand Venes Rolim Medeiros,

Natural product bioactivities and synthesis

We aimed to determine whether carvacryl acetate acts as a TRPA1 receptor agonist and its effects against irinotecan (CPT-11) induced intestinal mucositis in mice.TRPA1 structure was obtained from a protein databank, and the 3D structure of carvacryl acetate was determined. Appropriate binding conformations were discovered via automatic docking simulations. To determine the effect of carvacryl acetate in vivo, mice were treated with either DMSO 2%, CPT-11, carvacryl acetate followed by CPT-11, or HC-030031, a TRPA1 antagonist, followed by carvacryl acetate. Jejunum samples were taken and structural, inflammatory and antioxidant parameters were studied.Eight amino acids residues in TRPA1 established stable interactions with carvacryl acetate, which led to pharmacological efficacy against CPT-11-induced intestinal mucositis via reduction of both neutropenia and bacteremia, increase in villi height and crypt depth, decrease in pro-inflammatory cytokines (interleukin-1β, keratinocyte chemoattractant and tumour necrosis factor-α) and decrease in malondialdehyde and nitric oxide metabolite levels in the jejunum.Carvacryl acetate is a promising anti-inflammatory and antioxidant agent, a fact confirmed through observations of its interactions with TRPA1 in CPT-11-induced intestinal mucositis in mice.