: 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 thickening. 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.

A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization / Cerqua, Ida; Neukirch, Konstantin; Terlizzi, Michela; Granato, Elisabetta; Caiazzo, Elisabetta; Cicala, Carla; Ialenti, Armando; Capasso, Raffaele; Werz, Oliver; Sorrentino, Rosalinda; Seraphin, Denis; Helesbeux, Jean-Jacques; Cirino, Giuseppe; Koeberle, Andreas; Roviezzo, Fiorentina; Rossi, Antonietta. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 181:(2022), p. 106250. [10.1016/j.phrs.2022.106250]

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

Cerqua, Ida
Primo
;
Granato, Elisabetta;Caiazzo, Elisabetta;Cicala, Carla;Ialenti, Armando;Capasso, Raffaele;Cirino, Giuseppe;Roviezzo, Fiorentina
;
Rossi, Antonietta
2022

Abstract

: 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 thickening. 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.
2022
A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization / Cerqua, Ida; Neukirch, Konstantin; Terlizzi, Michela; Granato, Elisabetta; Caiazzo, Elisabetta; Cicala, Carla; Ialenti, Armando; Capasso, Raffaele; Werz, Oliver; Sorrentino, Rosalinda; Seraphin, Denis; Helesbeux, Jean-Jacques; Cirino, Giuseppe; Koeberle, Andreas; Roviezzo, Fiorentina; Rossi, Antonietta. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 181:(2022), p. 106250. [10.1016/j.phrs.2022.106250]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/885983
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 14
social impact