Developmental toxicity of aristolochic acid in developing zebrafish (danio rerio) embryos: Cardiovascular failure and inhibited caudal fin regeneration

Abstract

The study employed a green fluorescent vascular endothelium transgenic line, Tg (VEGFR2: GFP), to evaluate the effects of aristolochic acid (AA) at various concentrations on cardiovascular and fin imperfections in developing zebrafish embryos. The findings reveal that the intersegmental vessels (ISVs), dorsal longitudinal anastomotic vessels (DLAVs), and fin regeneration in the embryos were attenuated and underdeveloped in comparison to the control at 1, 5, 10, 20, 30, and 40 ?M/L concentrations of AA. At 48 hours post-fertilization (hpf), pericardial sac edema, yolk sac edema, and slight trunk curvature were detected in the surviving larvae at 10 and 20 ?M/L. These consequences were more pronounced at AA concentrations of 30 and 40 ?M/L. A gradual reduction in survival, hatching, heart rate, length, and diameter of ISVs and DLAVs was observed at 10, 20, 30, and 40 ?M/L when the embryos were 48 hpf. In addition, the fin redevelopment of the zebrafish embryos was also constrained in the treatment groups. The embryos exhibited heartbeats; however, blood circulation was terminated in response to the additive effect of AA at 10 and 20 ?M/L concentrations. Furthermore, at higher AA levels, the embryos did not hatch. Instead, they died. The present study verified that AA has a significant toxic effect on zebrafish embryos. These outcomes may add to the existing knowledge of the possible toxicological impacts of AA and pave the path toward the sustainable development of treatments that promote human health. ? 2021