Respiratory and Olfactory Cytotoxicity of Inhaled 2,3-Pentanedione in Sprague-Dawley Rats
Respiratory and Olfactory Cytotoxicity of Inhaled 2,3-Pentanedione in Sprague-Dawley Rats
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DOI：
10.1016/j.ajpath.2012.05.021
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发表时间：
2012-09-01
影响因子：
6
通讯作者：
Sriram, Krishnan
中科院分区：
文献类型：
--
作者：
Hubbs, Ann F.;Cumpston, Amy M.;Sriram, Krishnan
调味品相关肺病是一种潜在的致残性疾病，与暴露于α-二酮黄油调味品，双乙酰（2，3-丁二酮）有关的食品工业工人。为了研究另一种α-二酮调味剂2，3-戊二酮会导致气道损伤的假设，吸入空气、2，3-戊二酮（112、241、318或354 ppm）或双乙酰（240 ppm）6小时的大鼠在第二天处死。吸入2，3-戊二酮的大鼠发生坏死性鼻炎、气管炎和支气管炎，与丁二酮诱导的损伤相当。为了研究延迟毒性，额外的大鼠吸入318（范围，317.9-318.9）ppm 2，3-戊二酮6小时，并在暴露后0 - 2、12 - 14或18 - 20小时处死。上鼻呼吸道上皮损伤涉及细胞凋亡和坏死，其在暴露后12至14小时进行。嗅觉神经上皮损伤包括嗅觉神经元的损失，其显示相对于支持细胞的2，3-戊二酮代谢酶二羰基/L-木酮糖还原酶的表达降低。Caspase 3激活偶尔涉及嗅球（OB）中的突触的嗅神经束。另一组大鼠吸入270 ppm的2，3-戊二酮6小时41分钟，使用实时PCR显示OB、纹状体、海马和小脑中IL-6和一氧化氮合酶-2的表达增加，血管内皮生长因子A的表达减少。Claudin-1在OB和纹状体的表达增加。我们的结论是，2，3-戊二酮是一种呼吸道危害，也可以改变大脑中的基因表达。(Am J Pathol 2012，181：829-844; http：//dx·doi·org/10·1016/j·ajpath·2012·05·021）
Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the alpha-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another a-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain. (Am J Pathol 2012, 181:829-844; http://dx.doi.org/10.1016/j.ajpath.2012.05.021)