Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
Qilu Hospital of Shandong University, Jinan, China.
J Appl Toxicol. 2022 Dec;42(12):1978-1985. doi: 10.1002/jat.4368. Epub 2022 Aug 17.
The clinical use of clozapine (CLZ), an atypical antipsychotic drug, was affected by side effects, such as cardiotoxicity. We selected normally developing zebrafish embryos to explore the antagonism of salvianolic acid A (SAA) against clozapine-induced cardiotoxicity. Embryos were treated with CLZ and SAA, and zebrafish phenotypes were observed at 24 h, 48 h, 72 h, and 96 h after treatment. The observed phenotypes included heart shape, heart rate, and venous sinus-arterial bulb (SV-BA) interval. Real-time quantitative PCR was used to detect changes in the expression of genes involved in heart inflammation, oxidative stress, and apoptosis. The results showed that SAA relieved pericardial edema, increased heart rate, and reduced the SV-BA interval. The PCR results also showed that when the zebrafish embryos were incubated with SAA and CLZ for 96 h, the expression of il-1b and nfkb2 were significantly downregulated, the expression of sod1 and cat were significantly upregulated, and the expressions of mcl1a and mcl1b were significantly downregulated. In summary, SAA can antagonize clozapine-induced cardiotoxicity.
氯氮平（CLZ）是一种非典型抗精神病药物，其临床应用受到心脏毒性等副作用的影响。我们选择正常发育的斑马鱼胚胎来探索丹酚酸 A（SAA）对氯氮平诱导的心脏毒性的拮抗作用。将 CLZ 和 SAA 处理胚胎，并在处理后 24、48、72 和 96 小时观察斑马鱼表型。观察的表型包括心脏形状、心率和静脉窦-动脉球（SV-BA）间隔。实时定量 PCR 用于检测与心脏炎症、氧化应激和细胞凋亡相关基因的表达变化。结果表明，SAA 缓解心包水肿，增加心率，减少 SV-BA 间隔。PCR 结果还表明，当斑马鱼胚胎在 SAA 和 CLZ 中孵育 96 小时时，il-1b 和 nfkb2 的表达明显下调，sod1 和 cat 的表达明显上调，mcl1a 和 mcl1b 的表达明显下调。综上所述，SAA 可以拮抗氯氮平诱导的心脏毒性。
