1. Academic Validation
  2. Fenobucarb induces heart failure and cerebral hemorrhage in zebrafish

Fenobucarb induces heart failure and cerebral hemorrhage in zebrafish

  • Aquat Toxicol. 2019 Apr;209:34-41. doi: 10.1016/j.aquatox.2018.12.020.
Xiao-Yu Zhu 1 Bo Xia 2 Yu-Ying Wu 2 Hua Yang 3 Chun-Qi Li 4 Ping Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province 210009, PR China; Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province 310051, PR China.
  • 2 Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province 310051, PR China.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province 210009, PR China.
  • 4 Hunter Biotechnology, Inc, F1A, Building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province 310051, PR China. Electronic address: [email protected].
  • 5 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province 210009, PR China. Electronic address: [email protected].
Abstract

The potential risk and toxic mechanisms of fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) to Animals and humans have not been fully elucidated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 48 hpf (hour post fertilization, hpf) to 72 hpf. We found that BPMC induced severe heart failure with bradycardia, reduced heart contractions, cardiac output and blood flow dynamics;and myocardial Apoptosis. BPMC also induced cerebral hemorrhages and blood erythrocyte reduction in a dose-dependent manner. Also observed were increased ROS production and capase 9 and 3/7 activation. The mRNA levels of the ATPase-related gene (atp2a1l), calcium channel-related gene (cacna1ab), sodium channel-related gene (scn5Lab), potassium channel-related gene (kcnq1), the regulatory gene (tnnc1a) for cardiac troponin C, and several apoptosis-related genes were significantly downregulated in zebrafish following BPMC exposure. These results suggest that exposure to BPMC is a possible risk factor to cardiovascular and cerebrovascular systems in Animals.

Keywords

BPMC; Cerebral hemorrhage; Fenobucarb; Heart failure; Zebrafish.

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