Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish.

Du, Zheng‐Cai; Xia, Zhong‐Shang; Huang, Yan‐Feng; Peng, Yi; Cao, Bing‐Bing; Li, Chun‐Qi; Liang, Yun‐Fei; Zhao, Fang‐Hui; Zhang, Ming‐Zhe; Chen, Zhang‐Mei; Hou, Xiao‐Tao; Hao, Er‐Wei; Deng, Jia‐Gang

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti‐ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE‐induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose‐dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis. In this study, using yolk sac microinjection, we explored the cardiac dysfunction induced by exposure of CMSE in zebrafish and found that induced cardiac toxicity phenotypes including the pericardial edema and bradycardia, but had no effect on atrioventricular block. The decreased cardiac output in zebrafish was triggered by oxidative stress and neutrophil‐mediated cardiac inflammation. In addition, CMSE inhibited the calcium signaling pathway and cardiac muscle contraction pathway via the down‐regulation‐related genes of calcium channel and cardiac troponin C and decreased the protein level of cardiac contraction marker protein TNNT2.

ZEBRA danio embryos; ZEBRA danio; BRACHYDANIO; CARDIOTOXICITY; CHINESE medicine; FLOW velocity; METABOLITES; CARDIAC contraction

Journal of Applied Toxicology, 2021, Vol 41, Issue 8, p1222

0260-437X

Academic Journal

10.1002/jat.4108