The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity
Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene vi...
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Elsevier
2024-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324014647 |
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| author | Rongfang Yang Jiaxin Zhang Xiumei Xing Shiyuan Zhong Wenxue Li Lixian Wen Yuwei Zhang Hongwei Zhou Shen Chen Wen Chen Yongmei Xiao Liping Chen |
| author_facet | Rongfang Yang Jiaxin Zhang Xiumei Xing Shiyuan Zhong Wenxue Li Lixian Wen Yuwei Zhang Hongwei Zhou Shen Chen Wen Chen Yongmei Xiao Liping Chen |
| author_sort | Rongfang Yang |
| collection | DOAJ |
| description | Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo, MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity. |
| format | Article |
| id | doaj-art-beb2e2a3ff804ea69119eef539823787 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-beb2e2a3ff804ea69119eef5398237872024-12-07T08:24:38ZengElsevierEcotoxicology and Environmental Safety0147-65132024-12-01288117388The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicityRongfang Yang0Jiaxin Zhang1Xiumei Xing2Shiyuan Zhong3Wenxue Li4Lixian Wen5Yuwei Zhang6Hongwei Zhou7Shen Chen8Wen Chen9Yongmei Xiao10Liping Chen11Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Correspondence to: Department of Toxicology, School of Public Health, Sun Yat-sen University, China.Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo, MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity.http://www.sciencedirect.com/science/article/pii/S0147651324014647MetabolomicsTranscriptomics1-methylnicotinamideBenzeneHematotoxicity |
| spellingShingle | Rongfang Yang Jiaxin Zhang Xiumei Xing Shiyuan Zhong Wenxue Li Lixian Wen Yuwei Zhang Hongwei Zhou Shen Chen Wen Chen Yongmei Xiao Liping Chen The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity Ecotoxicology and Environmental Safety Metabolomics Transcriptomics 1-methylnicotinamide Benzene Hematotoxicity |
| title | The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity |
| title_full | The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity |
| title_fullStr | The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity |
| title_full_unstemmed | The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity |
| title_short | The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity |
| title_sort | involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene induced mouse hematotoxicity |
| topic | Metabolomics Transcriptomics 1-methylnicotinamide Benzene Hematotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324014647 |
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