Carey Stephan A, Plopper Charles G, Hyde Dallas M, Islam Zahidul, Pestka James J, Harkema Jack R
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA.
Toxicol Pathol. 2012 Aug;40(6):887-98. doi: 10.1177/0192623312444028. Epub 2012 May 2.
Satratoxin-G (SG) is a trichothecene mycotoxin of Stachybotrys chartarum, the black mold suggested to contribute etiologically to illnesses associated with water-damaged buildings. We have reported that intranasal exposure to SG evokes apoptosis of olfactory sensory neurons (OSNs) and acute inflammation in the nose and brain of laboratory mice. To further assess the potential human risk of nasal airway injury and neurotoxicity, we developed a model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans. Adult, male rhesus macaques received a single intranasal instillation of 20 µg SG (high dose, n = 3), or 5 µg SG daily for four days (repeated low dose, n = 3) in one nasal passage, and saline vehicle in the contralateral nasal passage. Nasal tissues were examined using light and electron microscopy and morphometric analysis. SG induced acute rhinitis, atrophy of the olfactory epithelium (OE), and apoptosis of OSNs in both groups. High-dose and repeated low-dose SG elicited a 13% and 66% reduction in OSN volume density, and a 14-fold and 24-fold increase in apoptotic cells of the OE, respectively. This model provides new insight into the potential risk of nasal airway injury and neurotoxicity caused by exposure to water-damaged buildings.
葡萄穗霉毒素-G(SG)是黄绿青霉产生的一种单端孢霉烯族霉菌毒素,这种黑色霉菌被认为在病因上与水浸建筑相关疾病有关。我们曾报道,经鼻暴露于SG会诱发实验小鼠嗅感觉神经元(OSN)凋亡以及鼻和脑的急性炎症。为进一步评估鼻腔气道损伤和神经毒性对人类的潜在风险,我们建立了一个猴子SG暴露模型,其鼻腔气道与人类的更为相似。成年雄性恒河猴在一侧鼻腔单次经鼻滴注20μg SG(高剂量,n = 3),或在对侧鼻腔每天滴注5μg SG,持续四天(重复低剂量,n = 3),对侧鼻腔滴注生理盐水作为对照。使用光学显微镜、电子显微镜和形态计量分析对鼻组织进行检查。两组中SG均诱发了急性鼻炎、嗅上皮(OE)萎缩和OSN凋亡。高剂量和重复低剂量SG分别使OSN体积密度降低了13%和66%,使OE凋亡细胞分别增加了14倍和24倍。该模型为接触水浸建筑所导致的鼻腔气道损伤和神经毒性的潜在风险提供了新的见解。