Fenobucarb induces heart failure and cerebral hemorrhage in zebrafish

Highlights: • We found that BPMC induced severe heart failure, with bradycardia, reduced heart contraction, cardiac output and blood flow dynamics as well as myocardial apoptosis. • BPMC induced cerebral hemorrhage and blood erythrocyte reduction in a dose-dependent manner. • Increased ROS production and capase 9 and 3/7 activation were observed. • The mRNA levels of 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 apoptosis-related genes were significantly downregulated in the zebrafish following BPMC exposure. • These results suggest that exposure to BPMC is a possible risk factor to cardiovascular and cerebrovascular systems in animals. -- 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 dynamicsand 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.