Background

Benzene is a toxic pollutant in industrial production that can cause serious damage to haematopoietic system, and the liver is the most important organ for benzene metabolism.

Objective

The aim of this study was to explore reliable biomarkers of benzene poisoning for an in-depth study of liver damage and its possible metabolic mechanisms through 4D label-free proteomics. We established a chronic benzene poisoning model in C57BL/6J mice via the gavage of a benzene/peanut oil mixture. Micebody weights and routine blood test results were recorded in detail. Mice livers were collected, and 4D label-free proteomics was used to identify the differentially expressed proteins.

Results

Compared with the control group, slow body weight gain, a reduction in whole blood cells and hepatocyte oedema were observed in the benzene poisoning group. A total of 303 differentially expressed proteins were identified with the screening conditions of a fold change > 2 (or < 1/2) and a P value < 0.05, of which 127 proteins were significantly upregulated and 176 proteins were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these proteins were associated mainly with metabolic pathways, metabolism of xenobiotics by cytochrome P450 and steroid hormone biosynthesis. We further selected three core proteins, Cytochrome P450 2B10, NADH dehydrogenase [quinone] 1 and Glutathione S-transferase Mu 3, for dual validation via immunoblotting and immunohistochemistry.

Conclusion

This study contributes to our understanding of benzene-induced hepatotoxicity and its metabolic mechanism in the liver.

中文翻译：

---

4D无标记蛋白质组分析慢性苯暴露小鼠的肝损伤机制

 背景

苯是工业生产中的有毒污染物，可对造血系统造成严重损害，而肝脏是苯代谢最重要的器官。

 客观的

本研究的目的是探索苯中毒的可靠生物标志物，通过4D无标记蛋白质组学深入研究肝损伤及其可能的代谢机制。我们通过灌胃苯/花生油混合物，在 C57BL/6J 小鼠中建立了慢性苯中毒模型。详细记录小鼠体重和血常规检查结果。收集小鼠肝脏，并使用4D无标记蛋白质组学来鉴定差异表达的蛋白质。

 结果

与对照组相比，苯中毒组体重增加缓慢，全血细胞减少，肝细胞水肿。以倍数变化> 2（或< 1/2）、 P值< 0.05的筛选条件，共鉴定出303个差异表达蛋白，其中127个蛋白显着上调，176个蛋白显着下调。京都基因和基因组百科全书分析表明，这些蛋白质主要与代谢途径、细胞色素 P450 的异生物质代谢和类固醇激素生物合成有关。我们进一步选择了三种核心蛋白，细胞色素 P450 2B10、NADH 脱氢酶 [醌] 1 和谷胱甘肽 S-转移酶 Mu 3，通过免疫印迹和免疫组织化学进行双重验证。

 结论

这项研究有助于我们了解苯引起的肝毒性及其在肝脏中的代谢机制。