Correlation between 3-MCPD-induced organ toxicity and oxidative stress response in male mice.
Correlation between 3-MCPD-induced organ toxicity and oxidative stress response in male mice.
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3-MCPD 诱导的雄性小鼠器官毒性与氧化应激反应之间的相关性。
DOI：
10.1016/j.fct.2019.110957
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Schultrich K
中科院分区：
文献类型：
--
作者：
Schultrich K
3-氯-1，2-丙二醇（3-MCPD）是一种食品污染物，已被列为非遗传毒性致癌物（2B类）。先前的研究表明，氧化应激可能在3-MCPD毒性中起作用。为了更详细地阐明3-MCPD介导的器官毒性的影响，采用了转基因报告小鼠，其含有在血红素加氧酶1（Hmox 1）启动子控制下的alacZ报告基因，该启动子对氧化应激有反应。在为期28天的喂食研究中，小鼠每天接受高达100 mg/kg体重的3-MCPD。随后，对来自不同器官的组织切片进行X-Gal染色，作为lacZ基因表达的读数。在小鼠肾脏中观察到蓝色染色呈剂量依赖性增加，仅在肾皮质中可见，但在肾髓质中不可见。此外，在睾丸生精小管的基底膜中以及特定的脑区域（小脑、中脑和脑桥）中检测到蓝色染色区域。值得注意的是，除了Hmox 1之外，许多Nrf 2依赖性靶基因的基因表达没有受到3-MCPD的严重影响。然而，在所有三个器官中，不可逆氧化的DJ-1蛋白（氧化应激的生物标志物）的量已经通过低剂量的3-MCPD显著增加。
3-Chloro-1,2-propanediol (3-MCPD) is a food contaminant which has been classified as a non-genotoxic carcinogen (category 2B). Previous studies suggested that oxidative stress might play a role in 3-MCPD toxicity. To elucidate the impact of 3-MCPD-mediated organ toxicity in more detail, transgenic reporter mice were employed which contain alacZreporter under the control of the heme oxygenase 1 (Hmox1) promoter which is responsive to oxidative stress. The mice received daily doses of up to 100 mg/kg body weight 3-MCPD per day in a 28-day feeding study. Subsequently, tissue slices from different organs were subjected to X-Gal staining as the readout forlacZgene expression. A dose-dependent increase of blue stain was observed in mouse kidney that was exclusively visible in the renal cortex but not in the renal medulla. Moreover, blue-stained regions were detected in the basal membrane of the seminiferous tubules in testes and also in specific brain regions (cerebellum, midbrain and pons). Notably, gene expression of a number of Nrf2-dependent target genes exceptHmox1was not severely affected by 3-MCPD. In all three organs, however, the amount of irreversibly oxidized DJ-1 protein, which is a biomarker for oxidative stress, was significantly increased already by low doses of 3-MCPD.
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DOI：
10.1016/j.fct.2015.06.002
发表时间：
2015
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
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期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
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作者：
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