Neurotoxic, Inflammatory, and Mucosecretory Responses in the Nasal Airways of Mice Repeatedly Exposed to the Macrocyclic Trichothecene Mycotoxin Roridin A: Dose-Response and Persistence of Injury
Neurotoxic, Inflammatory, and Mucosecretory Responses in the Nasal Airways of Mice Repeatedly Exposed to the Macrocyclic Trichothecene Mycotoxin Roridin A: Dose-Response and Persistence of Injury
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DOI：
10.1177/0192623310364026
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发表时间：
2010-04-01
影响因子：
1.5
通讯作者：
Harkema, Jack R.
中科院分区：
文献类型：
--
作者：
Corps, Kara N.;Islam, Zahidul;Harkema, Jack R.
在被水破坏的建筑物中遇到的大环毛霉毒素被认为是上呼吸道疾病的原因之一。在这里，作者描述了反复暴露于具有代表性的大环毛霉烯（roidin A， RA）对小鼠鼻气道的不良影响，并评估了这些影响的持久性。年轻、成年、雌性C57BL/6小鼠每天单次鼻内注射RA（0.4、2、10或50 μ g/kg体重[bw]）和生理盐水（50 μ g/kg体重）或生理盐水（对照组），持续3周或250 μ g/kg RA持续2周。最后一次给药24小时后进行的鼻气道组织病理学、免疫组织化学和形态计量学分析显示，最低效果水平为10 μ g/kg bw。类风湿关节炎暴露诱发了剂量依赖性的中性粒细胞性鼻炎，伴有粘液分泌过多、鼻过渡上皮和呼吸道上皮萎缩和脱落、嗅觉上皮萎缩和嗅觉感觉神经元（OSNs）丢失。在第二项研究中，对注射250 μ g/kg bw RA的小鼠进行了损伤持久性评估。3周后，鼻腔炎症和过多的腔内粘液消失，但嗅上皮（OE）仍有明显的OSN丢失。这些结果表明，鼻腔炎症、粘液分泌过多和嗅觉神经毒性可能是与短期、反复、空气中暴露于大环毛霉烯相关的重要不良健康影响。
Macrocyclic trichothecene mycotoxins encountered in water-damaged buildings have been suggested to contribute to illnesses of the upper respiratory tract. Here, the authors characterized the adverse effects of repeated exposures to roridin A (RA), a representative macrocyclic trichothecene, on the nasal airways of mice and assessed the persistence of these effects. Young, adult, female C57BL/6 mice were exposed to single daily, intranasal, instillations of RA (0.4, 2, 10, or 50 mu g/kg body weight [bw]) in saline (50 mu l) or saline alone (controls) over 3 weeks or 250 mu g/kg RA over 2 weeks. Histopathologic, immunohistochemical, and morphometric analyses of nasal airways conducted 24 hr after the last instillation revealed that the lowest-effect level was 10 mu g/kg bw. RA exposure induced a dose-dependent, neutrophilic rhinitis with mucus hypersecretion, atrophy and exfoliation of nasal transitional and respiratory epithelium, olfactory epithelial atrophy and loss of olfactory sensory neurons (OSNs). In a second study, the persistence of lesions in mice instilled with 250 mu g/kg bw RA was assessed. Nasal inflammation and excess luminal mucus were resolved after 3 weeks, but OSN loss was still evident in olfactory epithelium (OE). These results suggest that nasal inflammation, mucus hypersecretion, and olfactory neurotoxicity could be important adverse health effects associated with short-term, repeated, airborne exposures to macrocyclic trichothecenes.