Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling
Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very important for brain development. However, litt...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322004602 |
| _version_ | 1817985729016365056 |
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| author | Yuhang Xu Lingfei Luo Jingying Chen |
| author_facet | Yuhang Xu Lingfei Luo Jingying Chen |
| author_sort | Yuhang Xu |
| collection | DOAJ |
| description | Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very important for brain development. However, little information is available in the literature to show the toxicity of SMX to brain development. To study the SMX’s brain toxic effects and the related mechanisms, we exposed zebrafish embryos to SMX at different concentrations (0 ppm, 1 ppm, 25 ppm, 100 ppm and 250 ppm) and found that high concentration (250 ppm) of SMX would not only caused an abnormal in malformation rate, hatching rate, body length and survival rate of zebrafish embryos, but also lead to brain oedema. In addition, SMX also induced cerebral ischaemia, aggravates oxidative stress, and changes genes related to oxidative stress (sod1, cat, gpx4, and nrf2). Furthermore, ischaemia caused by SMX could promote ectopic angiogenesis in brain via activating the angiogenesis-related genes (vegfab, cxcr4a, cxcl12b) from 24 h to 53 h. Inhibition of VEGF signalling by SU5416, or inhibition of chemokine downstream PI3K signalling by LY294002, could rescue the brain capillaries toxicity and brain oedema induced by SMX. Our results provide new evidence for the brain toxicity of SMX and its residual danger in the environment and aquatic organisms. |
| first_indexed | 2024-04-14T00:01:42Z |
| format | Article |
| id | doaj.art-ef752bc95d834e5cbdd59a51b3bbceac |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-14T00:01:42Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-ef752bc95d834e5cbdd59a51b3bbceac2022-12-22T02:23:41ZengElsevierEcotoxicology and Environmental Safety0147-65132022-06-01238113620Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signallingYuhang Xu0Lingfei Luo1Jingying Chen2University of Chinese Academy of Sciences (Chongqing), Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Beibei, 400714 Chongqing, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, ChinaUniversity of Chinese Academy of Sciences (Chongqing), Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Beibei, 400714 Chongqing, China; Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, 400715 Chongqing, ChinaUniversity of Chinese Academy of Sciences (Chongqing), Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Beibei, 400714 Chongqing, China; Corresponding author.Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very important for brain development. However, little information is available in the literature to show the toxicity of SMX to brain development. To study the SMX’s brain toxic effects and the related mechanisms, we exposed zebrafish embryos to SMX at different concentrations (0 ppm, 1 ppm, 25 ppm, 100 ppm and 250 ppm) and found that high concentration (250 ppm) of SMX would not only caused an abnormal in malformation rate, hatching rate, body length and survival rate of zebrafish embryos, but also lead to brain oedema. In addition, SMX also induced cerebral ischaemia, aggravates oxidative stress, and changes genes related to oxidative stress (sod1, cat, gpx4, and nrf2). Furthermore, ischaemia caused by SMX could promote ectopic angiogenesis in brain via activating the angiogenesis-related genes (vegfab, cxcr4a, cxcl12b) from 24 h to 53 h. Inhibition of VEGF signalling by SU5416, or inhibition of chemokine downstream PI3K signalling by LY294002, could rescue the brain capillaries toxicity and brain oedema induced by SMX. Our results provide new evidence for the brain toxicity of SMX and its residual danger in the environment and aquatic organisms.http://www.sciencedirect.com/science/article/pii/S0147651322004602SulfamethoxazoleBrain capillaries toxicityBrain oedemaVEGFChemokine |
| spellingShingle | Yuhang Xu Lingfei Luo Jingying Chen Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling Ecotoxicology and Environmental Safety Sulfamethoxazole Brain capillaries toxicity Brain oedema VEGF Chemokine |
| title | Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling |
| title_full | Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling |
| title_fullStr | Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling |
| title_full_unstemmed | Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling |
| title_short | Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling |
| title_sort | sulfamethoxazole induces brain capillaries toxicity in zebrafish by up regulation of vegf and chemokine signalling |
| topic | Sulfamethoxazole Brain capillaries toxicity Brain oedema VEGF Chemokine |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322004602 |
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