Guoliang Chen,Juan Liu,Huiyun Wang,Mingxing Wang,Guixue Wang,Tingzhang Hu
SYP-3343 is a novel strobilurin fungicide with excellent and broad-spectrum antifungal activity , and its potential toxicity raises public health concerns. However, the vascular toxicity of SYP-3343 to zebrafish embryos is still not well understood. In the present study, we investigated the effects of SYP-3343 on vascular growth and its potential mechanism of action. SYP-3343 inhibited zebrafish endothelial cell (zEC) migration, altered nuclear morphology, and triggered abnormal vasculogenesis and zEC sprouting angiogenesis , resulting in angiodysplasia . RNA sequencing showed that SYP-3343 exposure altered the transcriptional levels of vascular development-related biological processes in zebrafish embryos including angiogenesis, sprouting angiogenesis, blood vessel morphogenesis , blood vessel development, and vasculature development. Whereas, the addition of NAC exerted an improvement effect on zebrafish vascular defects owing to SYP-3343 exposure. Additionally, SYP-3343 altered cell cytoskeleton and morphology, obstructed migration and viability, disrupted cell cycle progression, and depolarized mitochondrial membrane potential, as well as promoted apoptosis and reactive oxygen species (ROS) in HUVEC. SYP-3343 also caused an imbalance of the oxidation and antioxidant systems and irritated the alterations in the cell cycle- and apoptosis-related genes in HUVECs. Collectively, SYP-3343 has high cytotoxicity, possibly by up-regulating p53 and caspase3 expressions and bax/bcl-2 ratio via ROS, leading to malformed vascular development.
Guoliang Chen,Mingxing Wang,Panpan Zhu,Guixue Wang,Tingzhang Hu
As a newly-invented and highly-efficiency strobilurin fungicide , pyraoxystrobin (SYP-3343) has been recognized as a highly poisonous toxin for a variety of aquatic organisms. Nevertheless, the developmental toxicity and potential mechanism of SYP-3343 have not been well-documented. The results showed that SYP-3343 was relatively stable and maintained within the range of 20 % in 24 h, and the LC 50 value to embryos at 72 hpf was 17.13 μg/L. The zebrafish embryotoxicity induced by 1, 2, 4, and 8 μg/L SYP-3343 is demonstrated by repressive embryo incubation, enhancive mortality rate, abnormal heart rate, malformed morphological characteristic, and impaired spontaneous coiling, indicating SYP-3343 mostly exerted its toxicity in a dose- and time-dependent manner. Besides SYP-3343 was critically involved in regulating cell cycle, mitochondrial membrane potential, and reactive oxygen species production as well as zebrafish primary cells apoptosis, which can be mitigated using antioxidant N-acetyl- L -cysteine. A significant change occurred in total protein content, the biochemical indices, and antioxidant capacities owing to SYP-3343 exposure. Additionally, SYP-3343 altered the mRNA levels of heart development-, mitochondrial function-, and apoptosis-related genes in zebrafish embryos. These results indicated that SYP-3343 induced apoptosis accompanying reactive oxygen species-initiated mitochondrial dysfunction in zebrafish embryos.
危险品化学品经营许可证（带存储）