Plasma metabolomics study reveals the critical metabolic signatures for benzene-induced hematotoxicity

Guo, Xiaoli; Zhang, Lei; Wang, Jingyu; Zhang, Wei; Ren, Jing; Chen, Yujiao; Yan-lin, Zhang; Gao, Ai

doi:10.1172/jci.insight.154999

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…The results showed that exposure to benzene leads to alterations in carnitine transport, fatty acid metabolism, sulfur amino acid metabolism, glycolysis, gluconeogenesis, and branched-chain amino acid metabolism. Mono- and polyunsaturated and short-chain fatty acids are also significantly associated with S-phenylmercapturic acid and leukocytes, and reported as key mediators of benzene-induced hematotoxicity in the study by Guo et al (2022) [ 91 ].…”

Section: Resultsmentioning

confidence: 99%

Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity

et al. 2022

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Benzene is a human carcinogen whose exposure to concentrations below 1 ppm (3.19 mg.m−3) is associated with myelotoxic effects. The determination of biomarkers such as trans-trans muconic acid (AttM) and S-phenylmercapturic acid (SPMA) show exposure without reflecting the toxic effects of benzene. For this reason, in this study, the urinary metabolome of individuals exposed to low concentrations of benzene was investigated, with the aim of understanding the biological response to exposure to this xenobiotic and identifying metabolites correlated with the toxic effects induced by it. Ultra-efficient liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer (UHPLC-ESI-Q-ToF-MS) was used to identify metabolites in the urine of environmentally (n = 28) and occupationally exposed (n = 32) to benzene (mean of 22.1 μg.m−3 and 31.8 μg.m−3, respectively). Non-targeted metabolomics analysis by PLS-DA revealed nine urinary metabolites discriminating between groups and statistically correlated with oxidative damage (MDA, thiol) and genetic material (chromosomal aberrations) induced by the hydrocarbon. The analysis of metabolic pathways revealed important alterations in lipid metabolism. These results point to the involvement of alterations in lipid metabolism in the mechanisms of cytotoxic and genotoxic action of benzene. Furthermore, this study proves the potential of metabolomics to provide relevant information to understand the biological response to exposure to xenobiotics and identify early effect biomarkers.

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Section: Resultsmentioning

confidence: 99%

Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity

et al. 2022

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“…The basic characteristics (Supplementary Table S3) and hematological indicators of the subjects were described in our previous study. 28 In the present study, we obtained informed consent from all subjects, and the protocol was approved by the Ethics and Human Subject Committee of Capital Medical University (2017054).…”

Section: Methodsmentioning

confidence: 99%

Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity

Zhang,

Liu,

Zhang

et al. 2024

Gut Microbes

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Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus . Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.

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“…Internal standards were added to the test samples in order to monitor analytical variations during the entire sample preparation and analysis processes. 20…”

Section: Metabolomics Assaysmentioning

confidence: 99%

Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

et al. 2023

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Summary Amino acids in the bone marrow microenvironment (BMME) are a critical factor for multiple myeloma (MM) progression. Here, we have determined that proline is elevated in BMME of MM patients and links to poor prognosis in MM. Moreover, exogenous proline regulates MM cell proliferation and drug resistance. Elevated proline in BMME is due to bone collagen degradation and abnormal expression of the key enzyme of proline catabolism, proline dehydrogenase (PRODH). PRODH is downregulated in MM patients, mainly as a result of promoter hypermethylation with high expression of DNMT3b. Thus, overexpression of PRODH suppresses cell proliferation and drug resistance of MM and exhibits therapeutic potential for treatment of MM. Altogether, we identify proline as a key metabolic regulator of MM, unveil PRODH governing MM progression and provide a promising therapeutic strategy for MM treatment.

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Plasma metabolomics study reveals the critical metabolic signatures for benzene-induced hematotoxicity

Cited by 15 publications

References 46 publications

Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity

Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity

Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity

Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

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