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Therapeutic potential of α‐lipoic acid derivative, sodium zinc histidine dithiooctanamide, in a mouse model of allergic rhinitis
Author(s) -
Nakano Toshiaki,
Hsu LiWen,
Lai ChiaYun,
Takaoka Yuki,
Inomata Masafumi,
Kitano Seigo,
Chen ChaoLong,
Goto Shigeru
Publication year - 2017
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.22008
Subject(s) - medicine , ovalbumin , immunology , degranulation , immunoglobulin e , mast cell , immune system , allergic response , oxidative stress , allergy , allergic inflammation , pharmacology , antibody , endocrinology , receptor
Background Oxidative stress is involved in various diseases, including allergies. Several studies have pointed to the preventive and therapeutic potential of antioxidants in allergic disorders. However, little is known about the immunomodulatory effects of antioxidants in type I hypersensitivity. In this study we aimed to explore the impact of a water‐soluble antioxidant and α‐lipoic acid derivative, sodium zinc histidine dithiooctanamide (DHL‐HisZn), on mast‐cell‐ and T‐cell‐mediated allergic and immune responses both in vitro and in vivo. Methods The therapeutic impact of DHL‐HisZn on mast‐cell‐mediated type I hypersensitivity was evaluated by a mast‐cell degranulation assay using bone marrow‐derived mast cells and by a mouse model of ovalbumin (OVA)‐induced allergic rhinitis. The effect of DHL‐HisZn on the proportion of regulatory T cells (Tregs) was evaluated using flow cytometry. Results During the course of OVA‐induced allergic rhinitis in mice, serum nitrate was elevated, suggesting the involvement of oxidative stress in allergic responses. DHL‐HisZn not only suppressed mast‐cell degranulation but also ameliorated OVA‐induced nasal hypersensitivity, with significant suppression of serum nitrate. DHL‐HisZn treatment significantly suppressed OVA‐specific immunoglobulin E (IgE) but enhanced OVA‐specific IgG2a in OVA‐sensitized and nasal‐challenged mice. Furthermore, DHL‐HisZn treatment suppressed interleukin‐17 production in OVA‐stimulated splenocytes. Finally, we demonstrated the induction of Tregs by DHL‐HisZn in concanavalin A blasts. Conclusions These findings suggest that DHL‐HisZn may regulate mast‐cell‐, T‐helper 2 (Th2)‐, and Th17‐mediated allergic and immune responses by induction of Tregs.