A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization - Substances d'Origine Naturelle et Analogues Structuraux Accéder directement au contenu
Article Dans Une Revue Pharmacological Research Année : 2022

A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization

Ida Cerqua
  • Fonction : Auteur
Konstantin Neukirch
  • Fonction : Auteur
Michela Terlizzi
  • Fonction : Auteur
Elisabetta Granato
  • Fonction : Auteur
Elisabetta Caiazzo
  • Fonction : Auteur
Carla Cicala
  • Fonction : Auteur
Armando Ialenti
  • Fonction : Auteur
Raffaele Capasso
  • Fonction : Auteur
Oliver Werz
  • Fonction : Auteur
Rosalinda Sorrentino
  • Fonction : Auteur
Giuseppe Cirino
  • Fonction : Auteur
Andreas Koeberle
  • Fonction : Auteur
Fiorentina Roviezzo
  • Fonction : Auteur
Antonietta Rossi
  • Fonction : Auteur

Résumé

Benefits for vitamin E intake in diseases with inflammatory components have been described and related in part, to endogenously formed metabolites (long-chain metabolites, LCM). Here, we have evaluated the role of LCM in relieving asthma features. To this aim, the endogenous vitamin E metabolite α-13′-carboxychromanol (α-T-13′-COOH) that acts as potent 5-lipoxygenase inhibitor has been administered either intraperitoneally or by oral gavage to BALB/c mice sensitized by subcutaneous injection of ovalbumin (OVA). We also have taken advantage of the metabolically stable α-T-13′-COOH derivative α-amplexichromanol (α-AC). Intraperitoneal treatment with α-T-13'-COOH reduced OVA-induced airway hyperreactivity (AHR) as well as peri-bronchial inflammatory cell infiltration. α-AC was more efficacious than α-T-13'-COOH, as demonstrated by better control of AHR and in reducing subepithelial. Both compounds exerted their protective function by reducing pulmonary leukotriene C4 levels. Beneficial effects of α-AC were coupled to inhibition of the sensitization process, as indicated by a reduction of IgE plasma levels, lung mast cell infiltration and Th2 immune response. Metabololipidomics analysis revealed that α-AC raises the pulmonary levels of prostanoids, their degradation products, and 12/15-lipoxygenase metabolites. Following oral administration, the pharmacodynamically different profile in α-T-13′-COOH and α-AC was abrogated as demonstrated by a similar and improved efficacy in controlling asthma features as well as by metabololipidomics analysis. In conclusion, this study highlights a role for LCM and of vitamin E derivatives as pharmacologically active compounds that ameliorate asthmatic features and defines an important role for endogenous vitamin E metabolites in regulating immune response underlying the sensitization process.
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hal-03788166 , version 1 (22-09-2023)

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Ida Cerqua, Konstantin Neukirch, Michela Terlizzi, Elisabetta Granato, Elisabetta Caiazzo, et al.. A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization. Pharmacological Research, 2022, 181, pp.106250. ⟨10.1016/j.phrs.2022.106250⟩. ⟨hal-03788166⟩
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