The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency. Our previous study revealed the level of G6PD changed in wild type (WT) mice after benzene exposure. In this study, the pentose phosphate pathway (PPP) in regulation of benzene-induced hematotoxicity was...
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Elsevier
2021-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321009155 |
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| author | Tong Wang Hong Zhang Kun Wang Meng Cao Mengying Zhang Rongli Sun Yuepu Pu Juan Zhang |
| author_facet | Tong Wang Hong Zhang Kun Wang Meng Cao Mengying Zhang Rongli Sun Yuepu Pu Juan Zhang |
| author_sort | Tong Wang |
| collection | DOAJ |
| description | Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency. Our previous study revealed the level of G6PD changed in wild type (WT) mice after benzene exposure. In this study, the pentose phosphate pathway (PPP) in regulation of benzene-induced hematotoxicity was investigated and other potential pathways were discovered in a G6PD deficiency mouse model. WT and G6PD mutation (G6PDmut) mice were exposed to benzene (diluted in corn oil) at doses of 0 and 160 mg/kg by subcutaneous injection for 5 days/week, 4 weeks. Peripheral blood samples and bone marrow cells (BMCs) were obtained and measured. The levels of nicotinamide adenine dinucleotide phosphate (NADPH),reduced glutathione (GSH) and malondialdehyde (MDA) were detected and comet assay was analyzed for DNA damage in BMCs. Finally, RNA sequencing (RNA-seq) of BMCs was performed. The results showed that white blood cells decreased significantly in G6PDmut mice compared with WT mice after benzene treatment. The ratio of hematopoietic stem/progenitor cells significantly decreased in G6PDmut mice exposed to benzene. The reduction of NADPH and GSH revealed the effect on PPP with G6PD deficiency, which then caused the increase of MDA and DNA damage. Finally, RNA-seq results suggested potential genes including SHROOM4, CAMK2B and REN1 played potential roles of G6PD deficiency on benzene-induced hematotoxicity. Renin-angiotensin system and cAMP signaling pathway were potentially involved in the process. Our study provides a better understanding for the effects of G6PD deficiency on benzene-induced hematotoxicity. |
| first_indexed | 2024-12-16T06:52:08Z |
| format | Article |
| id | doaj.art-ea0d1189bedc4ad89d0f6db93696808a |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-16T06:52:08Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-ea0d1189bedc4ad89d0f6db93696808a2022-12-21T22:40:22ZengElsevierEcotoxicology and Environmental Safety0147-65132021-12-01226112803The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in miceTong Wang0Hong Zhang1Kun Wang2Meng Cao3Mengying Zhang4Rongli Sun5Yuepu Pu6Juan Zhang7Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaCorresponding author.; Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, ChinaGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency. Our previous study revealed the level of G6PD changed in wild type (WT) mice after benzene exposure. In this study, the pentose phosphate pathway (PPP) in regulation of benzene-induced hematotoxicity was investigated and other potential pathways were discovered in a G6PD deficiency mouse model. WT and G6PD mutation (G6PDmut) mice were exposed to benzene (diluted in corn oil) at doses of 0 and 160 mg/kg by subcutaneous injection for 5 days/week, 4 weeks. Peripheral blood samples and bone marrow cells (BMCs) were obtained and measured. The levels of nicotinamide adenine dinucleotide phosphate (NADPH),reduced glutathione (GSH) and malondialdehyde (MDA) were detected and comet assay was analyzed for DNA damage in BMCs. Finally, RNA sequencing (RNA-seq) of BMCs was performed. The results showed that white blood cells decreased significantly in G6PDmut mice compared with WT mice after benzene treatment. The ratio of hematopoietic stem/progenitor cells significantly decreased in G6PDmut mice exposed to benzene. The reduction of NADPH and GSH revealed the effect on PPP with G6PD deficiency, which then caused the increase of MDA and DNA damage. Finally, RNA-seq results suggested potential genes including SHROOM4, CAMK2B and REN1 played potential roles of G6PD deficiency on benzene-induced hematotoxicity. Renin-angiotensin system and cAMP signaling pathway were potentially involved in the process. Our study provides a better understanding for the effects of G6PD deficiency on benzene-induced hematotoxicity.http://www.sciencedirect.com/science/article/pii/S0147651321009155BenzeneG6PDHematotoxicityPentose phosphate pathwayRNA-sequencing |
| spellingShingle | Tong Wang Hong Zhang Kun Wang Meng Cao Mengying Zhang Rongli Sun Yuepu Pu Juan Zhang The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice Ecotoxicology and Environmental Safety Benzene G6PD Hematotoxicity Pentose phosphate pathway RNA-sequencing |
| title | The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice |
| title_full | The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice |
| title_fullStr | The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice |
| title_full_unstemmed | The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice |
| title_short | The effects of glucose-6-phosphate dehydrogenase deficiency on benzene-induced hematotoxicity in mice |
| title_sort | effects of glucose 6 phosphate dehydrogenase deficiency on benzene induced hematotoxicity in mice |
| topic | Benzene G6PD Hematotoxicity Pentose phosphate pathway RNA-sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321009155 |
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