4D label-free proteome analysis of the liver damage mechanism in mice with chronic benzene exposure

Abstract

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.