Evaluation of Neurodevelopmental Toxicity of Dianhydrogalactitol in Zebrafish
10.13748/j.cnki.issn1007-7693.20230751
- VernacularTitle:去水卫矛醇对斑马鱼神经发育毒性评价
- Author:
PENG Xiaoli
1
;
CAO Wen
1
;
LI Cheng
1
;
WEI Sijun
1
;
LIU Huagang
2
Author Information
1. Department of Pharmacy, International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530200, China
2. College of Pharmacy, Guangxi Medical University, Nanning 530022, China
- Publication Type:Journal Article
- Keywords:
dianhydrogalactitol;
zebrafish;
neurodevelopment;
dopaminergic neuron
- From:
Chinese Journal of Modern Applied Pharmacy
2023;40(15):2093-2099
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore dianhydrogalactitol(DAG)-induced neurodevelopmental toxicity and mechanisms in zebrafish embryos and larvae. METHODS On the basis of general toxicity evaluation, zebrafish embryos were exposed to DAG in groups, and the effects of DAG on zebrafish nerves and behaviors were observed by means of autonomic locomotor response and light stimulation response of juvenile fish; the effects of DAG on zebrafish brain tissues were observed by means of histopathological examination of brain and acridine orange staining. The relative expression of dopamine neuron-related genes(DAT, TH, GCH1) and neural inhibition/promotion of apoptosis-related genes(Bax, Bcl-2) was determined by real-time fluorescence quantitative PCR in zebrafish larvae. RESULTS DAG inhibited the voluntary movement of zebrafish under the 20, 40, 75 mg·L-1, and the inhibition rate of voluntary movement showed obvious concentration correlation; DAG inhibited the reaction speed of zebrafish under the 20, 40, 75 mg·L-1, and the rate of decrease of reaction ability showed concentration correlation; the brain tissue became smaller, but the tissue structure of zebrafish did not show any significant abnormality in the various concentration groups of DAG; acridine orange staining was used to detect the apoptosis of the overall embryonic cells of zebrafish, and it was found that the administration of DAG inhibited the apoptosis of zebrafish. Acridine orange staining was used to detect apoptosis in the whole embryonic cells of zebrafish, and it was found that the green fluorescence in the head of the administered group was more obvious than that in the control group, indicating that apoptosis increased, and apoptosis increased in a dose-dependent manner, which was in accordance with the apparent observation; DAG in 75, 150, 300, 425, 600 mg·L-1 of the experimental condition could lead to a downward regulation of the relative expression of mRNA of the genes related to the zebrafish juvenile dopaminergic neuron, DAT, TH and GCH1. The Bax/Bcl-2 relative mRNA expression was up-regulated with increasing drug concentration. CONCLUSION The neurodevelopmental toxicity of DAG in zebrafish embryos and juveniles may be related to the inhibition of dopaminergic neurons.
