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

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 LC 50 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 lg/mL for embryo, 7.5, 15 and 30 lg/mL for larvae) and control group (n ¼ 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 LC 50 value of KCH (24 or 45 lg/mL) was lower than KCW (1447 or 2011 lg/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 lg/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 lg/ 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.

Morphological, teratogenic and behavioral evaluations of Gelidium spinosum methanol extract on zebrafish embryos

“…GsME-treated zebrafish embryos exhibited significantly smaller eyes than untreated embryos (p < 0.05) in a dosage-dependent manner when compared against control groups. Previous investigations have also reported similar finding (Xia et al 2020).…”

O Pentáculo Do Bem Estar Como Instrumento De Avaliação Do Modo De Vida Na Atenção Primária a Saúde

“…A triagem de potenciais candidatos a terapias alternativas (utilizando produtos naturais) e/ou medicamentos, são realizadas desde os primórdios da pesquisa clínica, através de modelos experimentais, especialmente, de roedores (ratos e camundongos), Majoritariamente, pode-se observar que a principal utilização do modelo Zebrafish tem sido para avaliar toxicidade de novos compostos ou produtos naturais candidatos para aceitação regulatória (MOURA et al, 2019;SARASQUETE et al, 2018;HALLARE et al, 2014;GEBRELIBANOS et al, 2019;ALMEIDA et al, 2020;VECIANA et al, 2014;SAID et al, 2020;XIA et al, 2020;VEEREN et al, 2020;TEIXEIRA et al, 2020;CHANDRAMOHAN et al, 2019). Testes de toxicidade remetem ao estudo da capacidade de uma substância em causar danos aos organismos vivos, geralmente associada a concentração e duração da exposição, que envolve uma cascata de eventos relacionados a mecanismos de interação com órgãos-alvo, projetando efeitos nocivos que se manifestam se o xenobiótico atingir concentrações suficientes para desencadear algum efeito tóxico (MOURA et al;CHANDRAMOHAN et al, 2019;VEEREN et al, 2020).…”

Risk compounds, potential mechanisms and biomarkers of traditional Chinese medicine‐induced reproductive toxicity

“…were observed in larvae treated with KCH (K. coccinea hydroethanol extract) (15 or 30 μg/ml) (Xia et al, 2020). Another in vivo study using zebrafish has reported that honokiol-induced oxidative effect is related to the dosage.…”

“…Glycosides of Tripterygium wilfordii had significant impacts on reproduction‐related genes, such as Y chromosome micro‐deletion‐related gene Dzip1, germ cell apoptosis‐related gene Fas and signal transduction‐related gene Wnt4, damaging reproductivity in vivo (Zhang, Huang, et al, 2012). A hydroethanol extract of Kadsura coccinea activated genes that regulate developmental hepatotoxicity, oxidative stress and apoptosis in zebrafish, such as Bax, p53 and caspase‐3 (Xia et al, 2020). Honokiol induced developmental toxicity in the embryo via down‐regulating mRNA expression of SOD‐1, SOD‐2, cat, HO‐1 and Nrf2 (Li, Zhang, et al, 2019).…”

“…An in vivo study has demonstrated oxidative stress is responsible for developmental toxicity of K. coccinea consumption with zebrafish. Because increased ROS (89%), MDA concentrations (30%), apoptosis generation (62%) and decreased total superoxide dismutase (T‐SOD) activity (16%) were observed in larvae treated with KCH ( K. coccinea hydroethanol extract) (15 or 30 μg/ml) (Xia et al, 2020). Another in vivo study using zebrafish has reported that honokiol‐induced oxidative effect is related to the dosage.…”