Roots and stems of Kadsura coccinea extract induced developmental toxicity in zebrafish embryos/larvae through apoptosis and oxidative stress

五味子根茎提取物通过诱导细胞凋亡和氧化应激,对斑马鱼胚胎/幼体产生发育毒性。

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作者:Zhongshang Xia,Erwei Hao,Zhangmei Chen,Mingzhe Zhang,Yanting Wei,Man Wei,Xiaotao Hou,Zhengcai Du,Jiagang Deng

Abstract

Context: Although the roots and stems of Kadsura coccinea (Lem.) A. C. Smith. [Schisandraceae] are herbs and traditional foods in Li nationality, its toxicity remains unclear. Objective: To study developmental toxicity of K. coccinea consumption and explain underlying mechanisms. Materials and methods: Zebrafish were applied to assess LC50 values of hydroethanol extract (KCH) and water extract (KCW) of Kadsura coccinea. In further study, three concentrations groups of KCH (3.75, 7.5 and 15 μg/mL for embryo, 7.5, 15 and 30 μg/mL for larvae) and control group (n = 30) were administered. At specific stages of zebrafish development, spontaneous movement, hatching rate, etc., were measured. Gene expressions related to developmental toxicity were examined. Results: The LC50 value of KCH (24 or 45 μg/mL) was lower than KCW (1447 or 2011 μg/mL) in embryos or larvae. The inhibited spontaneous movement (20%), hatching rate (20%), body length (12%) and eye area (30%) were observed after KCH treatment. Moreover, the decreased liver areas (25%) and fluorescence intensity (33%), increased ALT (37%) and AST levels (42%) were found in larvae treated with KCH (30 μg/mL). The increased ROS (89%), MDA concentrations (30%), apoptosis generation (62%) and decreased T-SOD activity (16%) were also observed. The represented genes of developmental hepatotoxicity, oxidative stress and apoptosis in zebrafish were activated after KCH (15 or 30 μg/mL) treatment. Discussion and conclusions: These results demonstrate that KCH has developmental toxicity on zebrafish. Our study provides a scientific basis for further research on the toxicity of Kadsura coccinea.

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