γ-Tocopherol Attenuates Ozone-induced Exacerbation of Allergic Rhinosinusitis in Rats

Abstract

Compared to healthy subjects, individuals with allergic airway disease (e.g., asthma, allergic rhinitis) have enhanced inflammatory responses to inhaled ozone. We created a rodent model of ozone-enhanced allergic nasal responses in Brown Norway rats to test the therapeutic effects of the dietary supplement g-tocopherol (γT). Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0% or 0.5% OVA (in saline) on Days 1 and 2, and then exposed to 0 or 1 ppm ozone (eight hours/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg γT (p.o., in corn oil) on days 2 through 5, beginning twelve hours after the last OVA challenge. On Day 6, nasal tissues were collected for histological evaluation and mor-phometric analyses of intraepithelial mucosubstances (IM) and eosinophilic inflammation. Nasal septal tissue was microdissected and analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) for mucin glycoprotein 5AC (MUC5AC) expression levels. Histological analysis revealed mild to moderate eosinophil influx in the mucosa lining the nasal airways and maxillary sinus of OVA-challenged rats (eosinophilic rhinosinusitis). Ozone exposure of allergic rats further increased eosinophils in the maxillary sinus (400%), nasolacrimal duct (250%), and proximal midseptum (150%). Storage of intraepithelial mucosubstances (IM) was not significantly affected by OVA challenge in filtered air-exposed rats, but it was increased by ozone in the septum (45%) and maxillary sinus (55%) of allergic compared to control rats. Treatment with γT attenuated the ozone/ OVA-induced synergistic increases in IM and mucosal eosinophils in both nasal and paranasal airways. γ-Tocopherol also blocked OVA and ozone-induced MUC5AC gene expression. Together, these data describe a unique model of ozone enhancement of allergic rhinosinusitis and the novel therapeutic efficacy of a common supplement, γT, to inhibit ozone exacerbation of allergic airway responses.

Vitamin E and D regulation of allergic asthma immunopathogenesis

“…γ-Tocopherol scavenging of RNS may be beneficial for inflammation with increases in RNS such as neutrophilic inflammation that is induced by ozone or endotoxin in mice 23 . Consistent with this, reports indicate that supplementation with a mixture of tocopherols enriched for γ-tocopherol blocks acute endotoxin-stimulated or ozone-stimulated neutrophil inflammation in the rat and human lung 24–26 . In another study, γ-tocopherol supplementation reduced antigen induction of rat lung inflammation in which there was several fold more neutrophils than eosinophils 27 .…”

Two Faces of Vitamin E in the Lung

“…g-Tocopherol scavenging of reactive nitrogen species may be beneficial for inflammation with increases in reactive nitrogen species, such as neutrophilic inflammation that is induced by ozone in mice (22). Consistent with this, reports indicate that supplementation with a mixture of tocopherols that are enriched for g-tocopherol blocks acute endotoxin-stimulated or ozone-stimulated neutrophil inflammation in the rat and human lung (23)(24)(25). In another study, g-tocopherol supplementation reduced antigen induction of rat lung inflammation that was primarily neutrophils (26).…”

Composition and antioxidative activities of supercritical CO2-extracted oils from seeds and soft parts of northern berries

“…Studies have shown anti-inflammatory potential of γ-tocopherol and its metabolites probably via inhibition of cyclooxygenase-catalyzed synthesis of prostaglandin E 2 (PGE 2 ) (Reiter, Jiang, & Christen, 2007;Wagner, Jiang, Harkema, Illek, Patel, Ames et al, 2007;Jiang et al, 2008;Jiang, Moreland, Ames, & Yin, 2009;Wagner, Harkema, Jiang, Illek, Ames and Peden, 2009). The content of γ-tocopherol in raspberry seed oil is several times higher than the contents reported in commonly used vegetable oils (10-60 mg/100 g) (Gunstone & Harwood, 2007).…”