Laboratory of Experimental Physiology, School of Medicine, Aristotle University, Thessaloniki, Greece.
Int Forum Allergy Rhinol. 2013 Jul;3(7):543-9. doi: 10.1002/alr.21145. Epub 2013 Jan 10.
The pathophysiologic mechanism of allergy is dependent on the action of many redox-sensitive proinflammatory mediators. However, even though redox disturbances are believed to be a hallmark of inflammation, little is known of the effect of redox imbalance to the pathophysiology of allergic rhinitis. We thus opted to investigate the relation of oxidative stress and allergic rhinitis, through the utilization of a potent antioxidant substance (N-acetylcysteine [NAC]) in a rat model of allergic rhinitis and the evaluation of its action on specific markers of inflammation.
NAC (50 mg/kg and 250 mg/kg) was intraperitoneally administered to ovalbumin (OVA)-sensitized rats prior to intranasal challenge with OVA. Mucosal congregation of inflammatory cells (eosinophils and mast cells), mucosal expression of redox-sensitive enzymes (inducible nitric oxide synthase [iNOS] and cyclooxygenase 2 [COX-2]), and the blood levels of a key proinflammatory mediator (tumor necrosis factor-α [TNF-α]) were evaluated.
Intranasal OVA challenges lead to mucosal inflammation, induction of the mucosal expression of iNOS and COX-2 and elevation of TNF-α blood levels. NAC significantly inhibited accumulation of inflammatory cells and downregulated iNOS expression and TNF-α serum levels. The role of COX-2 appeared to be 2-fold and its expression was divergently modulated by NAC.
Our findings suggest that redox balance is involved in the pathophysiology of allergic rhinitis in rats and that NAC can potentially suppress the allergen-induced nasal inflammatory cascade. The investigation of the role of oxidative stress in atopy could help in the evaluation of the therapeutic potential of antioxidant substances in allergic diseases.
过敏的病理生理机制依赖于许多氧化还原敏感的促炎介质的作用。然而，尽管氧化还原失衡被认为是炎症的标志之一，但对于过敏性鼻炎的病理生理学中氧化还原失衡的影响知之甚少。因此，我们选择通过在过敏性鼻炎大鼠模型中使用一种有效的抗氧化物质（N-乙酰半胱氨酸[NAC]）来研究氧化应激与过敏性鼻炎的关系，并评估其对炎症特异性标志物的作用。
在卵清蛋白（OVA）致敏大鼠腹腔内给予 NAC（50mg/kg 和 250mg/kg）后，用 OVA 进行鼻内激发。评估炎症细胞（嗜酸性粒细胞和肥大细胞）在鼻黏膜的聚集、氧化还原敏感酶（诱导型一氧化氮合酶[iNOS]和环氧化酶 2[COX-2]）在鼻黏膜的表达以及关键促炎介质（肿瘤坏死因子-α[TNF-α]）的血液水平。
鼻内 OVA 激发导致鼻黏膜炎症，诱导 iNOS 和 COX-2 鼻黏膜表达增加，TNF-α 血清水平升高。NAC 显著抑制炎症细胞的积聚，并下调 iNOS 表达和 TNF-α 血清水平。COX-2 的作用似乎是双重的，其表达被 NAC 不同地调节。
我们的研究结果表明，氧化还原平衡参与了大鼠过敏性鼻炎的病理生理学过程，NAC 可能抑制过敏原诱导的鼻黏膜炎症级联反应。氧化应激在特应性中的作用的研究可能有助于评估抗氧化物质在过敏性疾病中的治疗潜力。
