Oxazolone (OXA) is a respiratory allergen in Brown Norway rats.
نویسندگان
چکیده
Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at relatively low doses in test animals, suggesting that it has also respiratory allergenic potential. The lack of human data on respiratory allergenic potential of OXA may be due to lack of significant inhalation exposure. Here, female Brown Norway rats (BN) were sensitized by two or five dermal applications of OXA at the same total dose of 3.75mg. Controls received vehicle. All animals were challenged by inhalation to 45mg/m(3) OXA on day 21 and necropsy was performed on day 22. All sensitized animals had increased serum IgE. OXA challenge decreased breathing frequency, and induced apnoeic breathing in the sensitized animals - a hallmark of respiratory allergy in our model. An exudative, granulocytic inflammation was observed primarily in the larynx of the sensitized and challenged rats. Microarray analysis of lung tissue, sampled 24h after challenge, revealed upregulation of several genes and activation of Gene Ontology (GO) pathways, which resembled more closely those found previously in lung tissue of rats sensitized and challenged by the respiratory allergen trimellitic anhydride than by the contact allergen dinitrochlorobenzene. The results indicate that the contact allergen OXA can also be a respiratory allergen, provided that it is inhaled. Its use as a model contact sensitizer must be reconsidered.
منابع مشابه
Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats.
To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness to acethylcholine was measured 24 h after ovalbumin (OVA) challenge, whereas br...
متن کاملRepeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling.
Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall. This study assessed the effect of repeated allergen exposure on ASM and epithelial cell deoxyribonucleic acid (DNA) synthesis, cell recruitment and airway wall pathology. Brown-Norway rats were sensitized and then exposed to ovalbumin or sal...
متن کاملRepeated allergen exposure changes collagen composition in airways of sensitised Brown Norway rats.
Increased or altered collagen deposition in the airway wall is one of the characteristics of airway remodelling in asthma. The mechanisms underlying this increase, and its functional consequences remain to be established further. Representative in vivo animal models might be useful in this respect. In the present study, collagen deposition after prolonged allergen exposure was characterised in ...
متن کاملThe contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat.
All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of ...
متن کاملRespiratory irritation by trimellitic anhydride in Brown Norway and Wistar rats.
Several acid anhydrides are known for their sensitizing and irritative properties. Since both irritation and respiratory allergy can cause changes of lung function, proper testing of allergen-dependent effects on the respiratory tract requires knowledge of the respiratory irritant effects. To study the latter effects, groups of female Brown Norway (BN) and Wistar rats were exposed for 30 min to...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Toxicology
دوره 290 1 شماره
صفحات -
تاریخ انتشار 2011