Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance
Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established...
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Elsevier
2023-08-01
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author | Lizhu Ye Xinhang Jiang Liping Chen Shen Chen Huiyao Li Rui Du Wei You Jing Peng Ping Guo Rui Zhang Hongyao Yu Guanghui Dong Daochuan Li Xue Li Wen Chen Xiumei Xing Yongmei Xiao |
author_facet | Lizhu Ye Xinhang Jiang Liping Chen Shen Chen Huiyao Li Rui Du Wei You Jing Peng Ping Guo Rui Zhang Hongyao Yu Guanghui Dong Daochuan Li Xue Li Wen Chen Xiumei Xing Yongmei Xiao |
author_sort | Lizhu Ye |
collection | DOAJ |
description | Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance. |
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spelling | doaj.art-aab88c5790be448399dbbc63c3fa2dc82023-08-16T04:26:28ZengElsevierEnvironment International0160-41202023-08-01178108113Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearanceLizhu Ye0Xinhang Jiang1Liping Chen2Shen Chen3Huiyao Li4Rui Du5Wei You6Jing Peng7Ping Guo8Rui Zhang9Hongyao Yu10Guanghui Dong11Daochuan Li12Xue Li13Wen Chen14Xiumei Xing15Yongmei Xiao16Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaInstitute of Mass Spectrometry and Atmospheric Environment, Jinan University, Guangzhou 510632, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Corresponding authors at: Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, China.Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Corresponding authors at: Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, China.Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.http://www.sciencedirect.com/science/article/pii/S0160412023003860BenzeneHigh-fat dietLipid depositionHematotoxicityExhaled breathBenzene metabolism |
spellingShingle | Lizhu Ye Xinhang Jiang Liping Chen Shen Chen Huiyao Li Rui Du Wei You Jing Peng Ping Guo Rui Zhang Hongyao Yu Guanghui Dong Daochuan Li Xue Li Wen Chen Xiumei Xing Yongmei Xiao Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance Environment International Benzene High-fat diet Lipid deposition Hematotoxicity Exhaled breath Benzene metabolism |
title | Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance |
title_full | Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance |
title_fullStr | Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance |
title_full_unstemmed | Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance |
title_short | Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance |
title_sort | moderate body lipid accumulation in mice attenuated benzene induced hematotoxicity via acceleration of benzene metabolism and clearance |
topic | Benzene High-fat diet Lipid deposition Hematotoxicity Exhaled breath Benzene metabolism |
url | http://www.sciencedirect.com/science/article/pii/S0160412023003860 |
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