New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease
Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play a role in its development. Triphenyl phosphate (TPHP) is commonly used in plastics and flame retardants. This study aims to investigate the potential impact of TPHP and its metaboli...
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002131 |
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| author | Ting Fang Qiaoyan Liu Xinxin Huangfu Hongkai Zhu Hongwen Sun Liming Chen |
| author_facet | Ting Fang Qiaoyan Liu Xinxin Huangfu Hongkai Zhu Hongwen Sun Liming Chen |
| author_sort | Ting Fang |
| collection | DOAJ |
| description | Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play a role in its development. Triphenyl phosphate (TPHP) is commonly used in plastics and flame retardants. This study aims to investigate the potential impact of TPHP and its metabolite diphenyl phosphate (DPHP) on diabetic kidney disease using various methods, including network toxicology, molecular docking, and cell experiments like CCK8 assay and real-time-PCR. The research examined the relationship between urinary DPHP levels and kidney function in American adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020. Additionally, the study explored the targets of action for TPHP and DPHP using network toxicity analysis, conducted protein interaction analysis, and explored the functional aspects of action through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Furthermore, the study identified key proteins involved in the action and conducted experimental verification by treating cells with TPHP and DPHP. Toxicity analysis showed that TPHP could cause dose-dependent toxicity in mouse podocyte clone 5 (MPC5) and mouse mesangial cells (MES13). The study also detected mRNA expression of core targets molecularly docked with TPHP and DPHP using real-time-PCR. The results indicated statistically significant regulation of most core targets by TPHP and DPHP in MPC5, MES13, and human kidney-2 cells. |
| format | Article |
| id | doaj-art-1e093df7ab674707a5f970afdadadb1c |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-1e093df7ab674707a5f970afdadadb1c2025-02-12T05:30:23ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117877New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney diseaseTing Fang0Qiaoyan Liu1Xinxin Huangfu2Hongkai Zhu3Hongwen Sun4Liming Chen5NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaMinistry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaMinistry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China; Correspondence to: No. 38 Tongyan Road, Jinnan District, Tianjin, PR China.NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China; Correspondence to: No.6 North Huanrui Road, Beichen District, Tianjin, PR China.Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play a role in its development. Triphenyl phosphate (TPHP) is commonly used in plastics and flame retardants. This study aims to investigate the potential impact of TPHP and its metabolite diphenyl phosphate (DPHP) on diabetic kidney disease using various methods, including network toxicology, molecular docking, and cell experiments like CCK8 assay and real-time-PCR. The research examined the relationship between urinary DPHP levels and kidney function in American adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020. Additionally, the study explored the targets of action for TPHP and DPHP using network toxicity analysis, conducted protein interaction analysis, and explored the functional aspects of action through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Furthermore, the study identified key proteins involved in the action and conducted experimental verification by treating cells with TPHP and DPHP. Toxicity analysis showed that TPHP could cause dose-dependent toxicity in mouse podocyte clone 5 (MPC5) and mouse mesangial cells (MES13). The study also detected mRNA expression of core targets molecularly docked with TPHP and DPHP using real-time-PCR. The results indicated statistically significant regulation of most core targets by TPHP and DPHP in MPC5, MES13, and human kidney-2 cells.http://www.sciencedirect.com/science/article/pii/S0147651325002131Network toxicityDiabetic kidney diseaseTriphenyl phosphateDiphenyl phosphate |
| spellingShingle | Ting Fang Qiaoyan Liu Xinxin Huangfu Hongkai Zhu Hongwen Sun Liming Chen New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease Ecotoxicology and Environmental Safety Network toxicity Diabetic kidney disease Triphenyl phosphate Diphenyl phosphate |
| title | New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| title_full | New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| title_fullStr | New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| title_full_unstemmed | New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| title_short | New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| title_sort | new insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease |
| topic | Network toxicity Diabetic kidney disease Triphenyl phosphate Diphenyl phosphate |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002131 |
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