Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos.
General anesthetics can cause neurological damage and long-term behavioral/cognitive impairment during fetal and early postnatal life. However, the adverse influence on embryo development induced by propofol is unclear. We used embryonic zebrafish to explore the effects of propofol on embryonic and...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0286391 |
| _version_ | 1797799858028937216 |
|---|---|
| author | Yali Ge Wenjuan Yuan Wenzhu Jia Zhongxia Guan Tianfeng Huang Yang Zhang Chengyi Song Yinggang Xiao Ju Gao |
| author_facet | Yali Ge Wenjuan Yuan Wenzhu Jia Zhongxia Guan Tianfeng Huang Yang Zhang Chengyi Song Yinggang Xiao Ju Gao |
| author_sort | Yali Ge |
| collection | DOAJ |
| description | General anesthetics can cause neurological damage and long-term behavioral/cognitive impairment during fetal and early postnatal life. However, the adverse influence on embryo development induced by propofol is unclear. We used embryonic zebrafish to explore the effects of propofol on embryonic and larval growth and development, and the related apoptotic mechanism. Zebrafish embryos were immersed in propofol (1, 2, 3, 4, and 5 μg/ml) dissolved in E3 medium from 6 to 48 hours post fertilization (hpf). The survival rate, locomotion, heart rate, hatchability, deformity rate, and body length were analyzed at defined stages. Terminal deoxynucleotidyl transferase nick-end-labeling was used to detect zebrafish embryo apoptosis, and the expression levels of apoptosis-related genes were determined using quantitative real-time reverse transcription PCR and whole-mount in situ hybridization. Larvae at 48 hpf were anesthetized by immersion in E3 culture medium containing 2 μg/ml propofol, the reasonable anesthetic concentration for zebrafish embryos, which caused significant caudal fin dysplasia, light pigmentation, edema, hemorrhage, and spinal deformity, and decreased the hatchability, body length, and heart rate. The numbers of apoptotic cells in propofol-treated 12, 48 and 72 hpf embryos increased significantly, and the mRNA expression levels of intrinsic apoptosis pathway-related casp3a, casp3b, casp9, and baxb genes were upregulated, mainly in the head and tail. Propofol decreased apoptosis in the head and back of 24 hpf zebrafish, which was consistent with the mRNA expression analysis. Our findings demonstrated that zebrafish embryos and larvae exposed to propofol experienced developmental toxicity, which correlated with the intrinsic apoptosis pathway with casp3a, casp3b, casp9, and baxb as the key genes. |
| first_indexed | 2024-03-13T04:26:18Z |
| format | Article |
| id | doaj.art-cdc1b9cd23ca4962ad8681cc66929389 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T04:26:18Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cdc1b9cd23ca4962ad8681cc669293892023-06-20T05:31:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028639110.1371/journal.pone.0286391Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos.Yali GeWenjuan YuanWenzhu JiaZhongxia GuanTianfeng HuangYang ZhangChengyi SongYinggang XiaoJu GaoGeneral anesthetics can cause neurological damage and long-term behavioral/cognitive impairment during fetal and early postnatal life. However, the adverse influence on embryo development induced by propofol is unclear. We used embryonic zebrafish to explore the effects of propofol on embryonic and larval growth and development, and the related apoptotic mechanism. Zebrafish embryos were immersed in propofol (1, 2, 3, 4, and 5 μg/ml) dissolved in E3 medium from 6 to 48 hours post fertilization (hpf). The survival rate, locomotion, heart rate, hatchability, deformity rate, and body length were analyzed at defined stages. Terminal deoxynucleotidyl transferase nick-end-labeling was used to detect zebrafish embryo apoptosis, and the expression levels of apoptosis-related genes were determined using quantitative real-time reverse transcription PCR and whole-mount in situ hybridization. Larvae at 48 hpf were anesthetized by immersion in E3 culture medium containing 2 μg/ml propofol, the reasonable anesthetic concentration for zebrafish embryos, which caused significant caudal fin dysplasia, light pigmentation, edema, hemorrhage, and spinal deformity, and decreased the hatchability, body length, and heart rate. The numbers of apoptotic cells in propofol-treated 12, 48 and 72 hpf embryos increased significantly, and the mRNA expression levels of intrinsic apoptosis pathway-related casp3a, casp3b, casp9, and baxb genes were upregulated, mainly in the head and tail. Propofol decreased apoptosis in the head and back of 24 hpf zebrafish, which was consistent with the mRNA expression analysis. Our findings demonstrated that zebrafish embryos and larvae exposed to propofol experienced developmental toxicity, which correlated with the intrinsic apoptosis pathway with casp3a, casp3b, casp9, and baxb as the key genes.https://doi.org/10.1371/journal.pone.0286391 |
| spellingShingle | Yali Ge Wenjuan Yuan Wenzhu Jia Zhongxia Guan Tianfeng Huang Yang Zhang Chengyi Song Yinggang Xiao Ju Gao Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. PLoS ONE |
| title | Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. |
| title_full | Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. |
| title_fullStr | Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. |
| title_full_unstemmed | Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. |
| title_short | Apoptotic mechanism of propofol-induced developmental toxicity in zebrafish embryos. |
| title_sort | apoptotic mechanism of propofol induced developmental toxicity in zebrafish embryos |
| url | https://doi.org/10.1371/journal.pone.0286391 |
| work_keys_str_mv | AT yalige apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT wenjuanyuan apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT wenzhujia apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT zhongxiaguan apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT tianfenghuang apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT yangzhang apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT chengyisong apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT yinggangxiao apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos AT jugao apoptoticmechanismofpropofolinduceddevelopmentaltoxicityinzebrafishembryos |