Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone).
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Basu P, Ghosh RN, Grove LE, Klei L, Barchowsky A
Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone).
Environ Health Perspect. 2008 Apr;116(4):520-3. doi: 10.1289/ehp.10885.
- PubMed ID
- 18414637 [ View in PubMed]
- Abstract
BACKGROUND: Roxarsone (3-nitro-4-hydroxy benzene arsonic acid) is an arsenic compound widely used in the poultry industry as a feed additive to prevent coccidiosis, stimulate growth, and to improve tissue pigmentation. Little is known about the potential human health effects from roxarsone released into the environment from chicken waste or from residual compound in chicken products. OBJECTIVE: The growth potentiation and enhanced tissue pigmentation suggest that low levels of roxarsone exposure may have an angiogenic potential similar to that of inorganic arsenite (As(III)). The goal of this investigation was to test the hypothesis described above using cultured human aortic and lung microvascular endothelial cells in high-content imaging tube-forming assays and begin developing a molecular level understanding of the process. METHODS: We used a three-dimensional Matrigel assay for probing angiogenesis in cultured human endothelial cells, and a polymerase chain reaction (PCR) array to probe the gene changes as a function of roxarsone or As(III) treatment. In addition, we used Western blot analysis for changes in protein concentration and activation. RESULTS: Roxarsone was found to exhibit a higher angiogenic index than As(III) at lower concentrations. Increased endothelial nitric oxide synthase (eNOS) activity was observed for roxarsone but not for As(III)-induced angiogenesis. However, As(III) caused more rapid and pronounced phosphorylation of eNOS. Quantitative PCR array on select genes revealed that the two compounds have different and often opposite effects on angiogenic gene expression. CONCLUSIONS: The results demonstrate that roxarsone and As(III) promote angiogenic phenotype in human endothelial cells through distinctly different signaling mechanisms.
DrugBank Data that Cites this Article
- Drugs
- Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Arsenic trioxide Approved Investigational CNMD 11061 downregulated arsenic trioxide results in decreased expression of CNMD mRNA 13q14.3 Arsenic trioxide Approved Investigational CXCL9 4283 downregulated arsenic trioxide results in decreased expression of CXCL9 mRNA 4q21.1 Arsenic trioxide Approved Investigational HGF 3082 upregulated arsenic trioxide results in increased expression of HGF mRNA 7q21.11 Arsenic trioxide Approved Investigational IGF1 3479 upregulated arsenic trioxide results in increased expression of IGF1 mRNA 12q23.2 Roxarsone Vet Approved ANGPT1 284 downregulated Roxarsone results in decreased expression of ANGPT1 mRNA 8q23.1 Roxarsone Vet Approved CNMD 11061 downregulated Roxarsone results in decreased expression of CNMD mRNA 13q14.3 Roxarsone Vet Approved CXCL9 4283 downregulated Roxarsone results in decreased expression of CXCL9 mRNA 4q21.1 Roxarsone Vet Approved HGF 3082 upregulated Roxarsone results in increased expression of HGF mRNA 7q21.11 Roxarsone Vet Approved LEP 3952 downregulated Roxarsone results in decreased expression of LEP mRNA 7q32.1 Roxarsone Vet Approved PLG 5340 downregulated Roxarsone results in decreased expression of PLG mRNA 6q26