Yoon Jin-Ha, Seo Heung-Sik, Lee Jinsoo, Moon Changjong, Lee Kyuhong
1 The Institute for Occupational Health, Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
2 Inhalation Toxicology Research Center, Korea Institute of Toxicology, Jeonbuk, Korea.
Toxicol Ind Health. 2016 Nov;32(11):1910-1920. doi: 10.1177/0748233715599087. Epub 2016 Jul 9.
Toluene is an organic solvent that is used in various industrial applications. Despite its usefulness, toluene has toxic effects on the brain and is a substance that is commonly abused. Toluene causes behavioral and functional abnormalities such as decreased memory capacity, cognitive impairment, and depression-like symptoms. However, the target sites and toxic mechanisms of inhaled toluene in the brain are poorly understood. In this study, we subjected Sprague-Dawley (SD) rats to acute high-level toluene exposure (7000 ppm) to investigate its neuronal toxicity, and in particular, its effect on neurogenesis in the hippocampus. In order to assay the effects of inhaled toluene on hippocampal neurogenesis, we measured the levels of neurogenesis markers Ki-67 and doublecortin (DCX) in the hippocampus 1, 2, 5, and 8 days after cessation of toluene exposure. In addition to assaying clinical signs, body weight, and bronchoalveolar lavage fluid, the liver, lungs, and kidneys were subjected to histopathological examination to investigate the toxic effects of high-level toluene exposure. Although abnormal neurological signs were observed after toluene exposure, these disappeared within 24 h and no toluene-related toxicological effects were observed in the liver, lungs, or kidneys. The animals exposed to toluene showed significantly decreased hippocampal neurogenesis, which persisted until the 8th and final day of measurement. Thus, acute high-level toluene exposure inhibited hippocampal neurogenesis and produced transient abnormal neurological signs, but did not produce toxicity in the other organs studied.
甲苯是一种有机溶剂，用于各种工业应用。尽管其有用性，但甲苯对大脑有毒性作用，是一种常见的滥用物质。甲苯会导致行为和功能异常，如记忆能力下降、认知障碍和类似抑郁的症状。然而，吸入的甲苯在大脑中的靶位点和毒性机制尚不清楚。在本研究中，我们让Sprague-Dawley（SD）大鼠急性高剂量暴露于甲苯（7000 ppm），以研究其神经毒性，特别是对海马体神经发生的影响。为了测定吸入甲苯对海马体神经发生的影响，我们在停止甲苯暴露后的第1、2、5和8天测量了海马体中神经发生标记物Ki-67和双皮质素（DCX）的水平。除了测定临床体征、体重和支气管肺泡灌洗液外，还对肝脏、肺和肾脏进行了组织病理学检查，以研究高剂量甲苯暴露的毒性作用。尽管在甲苯暴露后观察到异常神经体征，但这些体征在24小时内消失，并且在肝脏、肺或肾脏中未观察到与甲苯相关的毒理学效应。暴露于甲苯的动物海马体神经发生显著减少，这种减少一直持续到测量的第8天也是最后一天。因此，急性高剂量甲苯暴露抑制了海马体神经发生并产生了短暂的异常神经体征，但在所研究的其他器官中未产生毒性。
