Gamma-tocopherol attenuates ozone-induced exacerbation of allergic rhinosinusitis in rats.
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 gamma-tocopherol (gammaT). 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 gammaT (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 morphometric 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 gammaT attenuated the ozone/ OVA-induced synergistic increases in IM and mucosal eosinophils in both nasal and paranasal airways. gamma-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, gammaT, to inhibit ozone exacerbation of allergic airway responses.
Wagner
James G
JG
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA. wagnerja@msu.edu
Harkema
Jack R
JR
Jiang
Qing
Q
Illek
Beate
B
Ames
Bruce N
BN
Peden
David B
DB
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D004804:Eosinophils / Q000502:physiology; D008297:Male; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009296:Nasal Cavity / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000378:metabolism; D024504:gamma-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D010126:Ozone; D024504:gamma-Tocopherol; D010047:Ovalbumin