Acute toxicity and teratogenicity of alpha-mangostin in zebrafish embryos

摘要

alpha-Mangostin is the most active compound derived from the pericarps of mangosteen. A number of studies have reported its anticancer activity. However, only a few studies have investigated the toxicity of this compound; moreover, the teratogenicity of alpha-mangostin has not been reported. In this study, we evaluated the effects of alpha-mangostin on the development of zebrafish embryos. The exposure of zebrafish embryos to alpha-mangostin for 72 h dose-dependently induced mortality and abnormal development. The derived LC50 value of alpha-mangostin to zebrafish embryos at 72 h was 5.75 +/- 0.26 mu mol/L. We observed teratogenic effects in alpha-mangostin-treated embryos, characterized by axis malformation, bent tail, pericardial edema, yolk sac edema, sluggish circulation, and heart malformation. The percentages of the malformed embryos were 78.79% and 100% at 4.5 and 6 mu M, respectively. alpha-Mangostin exposure also caused hemostasis in the ducts of Cuvier and a decreased heart rate in zebrafish embryos at 48 and 72 h post-fertilization. These results indicated that alpha-mangostin induced cardiac dysfunction in zebrafish embryos. In addition, a sub-lethal concentration and a lethal concentration (3 and 6 mu M, respectively) were used to assess the compound effects on oxidative stress and embryonic erythropoiesis. alpha-Mangostin was found to decrease the level of reactive oxygen species (ROS) in zebrafish embryos. Furthermore, hemoglobin staining revealed a decrease in hemoglobin, which suggested that alpha-mangostin disrupted embryonic erythropoiesis in zebrafish. To our knowledge, the results of this study, for the first time, demonstrated that alpha-mangostin was potentially teratogenic and could disrupt embryonic ROS balance and erythropoiesis.