Acute toxicity and teratogenicity of α-mangostin in zebrafish embryos

Abstract

α-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 α-mangostin has not been reported. In this study, we evaluated the effects of α-mangostin on the development of zebrafish embryos. The exposure of zebrafish embryos to α-mangostin for 72 h dose-dependently induced mortality and abnormal development. The derived LC₅₀ value of α-mangostin to zebrafish embryos at 72 h was 5.75 ± 0.26 μmol/L. We observed teratogenic effects in α-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 μM, respectively. α-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 α-mangostin induced cardiac dysfunction in zebrafish embryos. In addition, a sub-lethal concentration and a lethal concentration (3 and 6 μM, respectively) were used to assess the compound effects on oxidative stress and embryonic erythropoiesis. α-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 α-mangostin disrupted embryonic erythropoiesis in zebrafish. To our knowledge, the results of this study, for the first time, demonstrated that α-mangostin was potentially teratogenic and could disrupt embryonic ROS balance and erythropoiesis.

Impact statement

α-Mangostin has been reported to have anticancer properties both in vitro and in vivo models. Although there are several studies that evaluated the toxicity of the compound in rodent models, we are the first to evaluate the teratogenicity of α-mangostin. In the present work, we found that α-mangostin induced mortality and malformations in zebrafish embryos. In addition, we exhibited that the compound also disrupted the reactive oxygen species and hemoglobin levels. These findings suggest that α-mangostin may possibly cause the same adverse effects on human health. The mechanisms of these toxicological effects of the compound will be further elucidated and the effects found in zebrafish embryos need to be verified in other animal models.