US Environmental Protection Agency, Chapel Hill, NC, USA.
Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Inhal Toxicol. 2021 May-Jul;33(6-8):268-274. doi: 10.1080/08958378.2021.1989092. Epub 2021 Nov 9.
Several mechanisms have been proposed for the biological effect of diacetyl. We tested the postulate that animal and cell exposures to diacetyl are associated with a disruption in iron homeostasis.
Male, Sprague-Dawley rats were intratracheally-instilled with either distilled water or diacetyl. Seven days after treatment, animals were euthanized and the lungs removed, fixed, and embedded. Sections were cut and stained for iron, collagen, and ferritin. Human epithelial (BEAS-2B) and monocytic (THP-1) cells were exposed to ferric ammonium citrate (FAC), diacetyl, and both FAC and diacetyl. Cell non-heme iron concentrations and ferritin levels were quantified using inductively coupled plasma optical emission spectroscopy and an immunoassay respectively.
After exposure of animals to diacetyl, there were airway polypoid lesions which stained positively for both iron and the intracellular storage protein ferritin. Trichrome stain showed a deposition of collagen immediately adjacent to accumulated metal following diacetyl exposure. In cell exposures, FAC increased non-heme iron concentration but co-incubations of FAC and diacetyl elevated levels to significantly greater values. Levels of ferritin were increased with exposures of BEAS-2B and THP-1 cells to FAC but were similarly greater after co-exposure with FAC and diacetyl.
Results of animal and cell studies support a disruption of iron homeostasis by diacetyl. It is proposed that, following internalization, diacetyl complexes intracellular sources of iron. The cell recognizes a loss of its requisite iron to diacetyl and imports greater concentrations of the metal.
已经提出了几种二乙酰的生物学效应机制。我们检验了以下假设，即动物和细胞暴露于二乙酰会导致铁稳态失调。
雄性 Sprague-Dawley 大鼠通过气管内滴注蒸馏水或二乙酰进行处理。处理 7 天后，处死动物并取出肺脏，固定并包埋。切取切片并用铁、胶原和铁蛋白染色。将人上皮（BEAS-2B）和单核（THP-1）细胞暴露于柠檬酸铁铵（FAC）、二乙酰和 FAC 与二乙酰的混合物中。使用电感耦合等离子体光发射光谱法和免疫测定法分别定量细胞非血红素铁浓度和铁蛋白水平。
动物暴露于二乙酰后，气道出现多瘤样病变，铁和细胞内储存蛋白铁蛋白均呈阳性染色。三原色染色显示，二乙酰暴露后，紧邻金属积累处有胶原沉积。在细胞暴露中，FAC 增加了非血红素铁浓度，但 FAC 和二乙酰的共孵育将其水平升高至显著更高的值。BEAS-2B 和 THP-1 细胞暴露于 FAC 会增加铁蛋白水平，但与 FAC 和二乙酰共暴露时则增加更多。
动物和细胞研究的结果支持二乙酰对铁稳态的破坏。据推测，二乙酰内化后与细胞内的铁源结合。细胞识别到其必需的铁被二乙酰消耗，并导入更多的金属。
