scholarly journals Involvement of Nrf2-HO-1/JNK-Erk Signaling Pathways in Aconitine-Induced Developmental Toxicity, Oxidative Stress, and ROS-Mitochondrial Apoptosis in Zebrafish Embryos

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Xia ◽  
Shuo Gao ◽  
Samuel Rajendran Rapael Gnanamuthu ◽  
Kaiyan Zhuang ◽  
Zhenzhen Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Developmental Toxicity ◽  
Brain Regions ◽  
High Dose ◽  
Zebrafish Embryos ◽  
Mitochondrial Apoptosis ◽  
Diterpenoid Alkaloids ◽  
High Concentration ◽  
Sod Activity ◽  
Underlying Mechanisms

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from Aconitum plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 μM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 μM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (Nrf2, HO-1, Cat, and Sod-1) Erk1/2 and Bcl-2 were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (Bad, Bax, Cyto C, Casp-9, and Casp-3) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.

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

2020 ◽  
Vol 58 (1) ◽  
pp. 1294-1301
Author(s):  
Zhongshang Xia ◽  
Erwei Hao ◽  
Zhangmei Chen ◽  
Mingzhe Zhang ◽  
Yanting Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Developmental Toxicity ◽  
Zebrafish Embryos ◽  
Kadsura Coccinea ◽  
And Oxidative Stress

Isoliquiritigenin triggers developmental toxicity and oxidative stress–mediated apoptosis in zebrafish embryos/larvae via Nrf2-HO1/JNK-ERK/mitochondrion pathway

Chemosphere ◽  
2020 ◽  
Vol 246 ◽  
pp. 125727 ◽  
Author(s):  
Zhenzhen Song ◽  
Yun Zhang ◽  
Huazheng Zhang ◽  
R. Samuel Rajendran ◽  
Rongchun Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Developmental Toxicity ◽  
Zebrafish Embryos ◽  
And Oxidative Stress

scholarly journals Toxicity Reduction of Euphorbia kansui Stir-Fried with Vinegar Based on Conversion of 3-O-(2′E,4′Z-Decadi-enoyl)-20-O-acetylingenol

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3806 ◽  
Author(s):  
Qiao Zhang ◽  
Yi Zhang ◽  
Shi-Kang Zhou ◽  
Kan Wang ◽  
Min Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Developmental Toxicity ◽  
Underlying Mechanism ◽  
Severe Toxicity ◽  
Sod Activity ◽  
Mechanisms Of Toxicity ◽  
Toxicity Reduction ◽  
Euphorbia Kansui ◽  
The Difference ◽  
Underlying Mechanisms

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

scholarly journals Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals

2019 ◽  
Vol 20 (5) ◽  
pp. 1065 ◽  
Author(s):  
Elisabet Teixidó ◽  
Marta Barenys ◽  
Ester Piqué ◽  
Joan Llobet ◽  
Jesús Gómez-Catalán
Keyword(s):  
Oxidative Stress ◽  
Developmental Toxicity ◽  
Environmental Pollutants ◽  
Cardiovascular Effects ◽  
Zebrafish Embryos ◽  
Oxidative Potential ◽  
Antioxidant Genes ◽  
Aryl Hydrocarbon ◽  
Low Concentrations ◽  
Pericardial Edema

The developing cardiovascular system of zebrafish is a sensitive target for many environmental pollutants, including dioxin-like compounds and pesticides. Some polychlorinated biphenyls (PCBs) can compromise the cardiovascular endothelial function by activating oxidative stress-sensitive signaling pathways. Therefore, we exposed zebrafish embryos to PCB126 or to several redox-modulating chemicals to study their ability to modulate the dysmorphogenesis produced by PCB126. PCB126 produced a concentration-dependent induction of pericardial edema and circulatory failure, and a concentration-dependent reduction of cardiac output and body length at 80 hours post fertilization (hpf). Among several modulators tested, the effects of PCB126 could be both positively and negatively modulated by different compounds; co-treatment with α-tocopherol (vitamin E liposoluble) prevented the adverse effects of PCB126 in pericardial edema, whereas co-treatment with sodium nitroprusside (a vasodilator compound) significantly worsened PCB126 effects. Gene expression analysis showed an up-regulation of cyp1a, hsp70, and gstp1, indicative of PCB126 interaction with the aryl hydrocarbon receptor (AhR), while the transcription of antioxidant genes (sod1, sod2; cat and gpx1a) was not affected. Further studies are necessary to understand the role of oxidative stress in the developmental toxicity of low concentrations of PCB126 (25 nM). Our results give insights into the use of zebrafish embryos for exploring mechanisms underlying the oxidative potential of environmental pollutants.

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

2016 ◽  
Vol 55 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Miao Hu ◽  
Nan Hu ◽  
Dexin Ding ◽  
Weichao Zhao ◽  
Yongfu Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gamma Irradiation ◽  
Developmental Toxicity ◽  
Zebrafish Embryos ◽  
And Oxidative Stress

scholarly journals N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Jiying Jiang ◽  
Shuna Yu ◽  
Zhengchen Jiang ◽  
Cuihong Liang ◽  
Wenbo Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Mitochondrial Apoptosis ◽  
Sod Activity ◽  
Stress Injury ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

scholarly journals Icaritin protects SH-SY5Y cells transfected with TDP-43 by alleviating mitochondrial damage and oxidative stress

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11978
Author(s):  
Yongjian Zhou ◽  
Nanqu Huang ◽  
Yuanyuan Li ◽  
Zhisheng Ba ◽  
Yanjun Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Cell Damage ◽  
Mitochondrial Damage ◽  
Atp Content ◽  
Sod Activity ◽  
Mda Content ◽  
Copper Zinc ◽  
Total Antioxidative Capacity ◽  
Underlying Mechanisms

Background The aim of this study was to investigate the effect of icaritin (ICT) on TAR DNA-binding protein 43 (TDP-43)-induced neuroblastoma (SH-SY5Y) cell damage and to further explore its underlying mechanisms. Methods To investigate the possible mechanism, TDP-43 was used to induce SH-SY5Y cell injury. Cell viability was evaluated by the CCK-8 assay. The mitochondrial membrane potential (MMP) was determined with JC-1. The expression levels of TDP-43 and cytochrome C (CytC) were measuring by Western blotting. Changes in adenosine 5′-triphosphate (ATP) content, total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected with specific kits. Results The results showed that ICT reduced the cell damage induced by TDP-43. ICT reduced the expression level of TDP-43; increased ATP content and the MMP; decreased CytC expression; increased T-AOC and GSH-Px, total SOD (T-SOD), copper/zinc SOD (CuZn-SOD), and manganese SOD (Mn-SOD) activity; and decreased MDA content. Conclusions The results suggest that ICT has a protective effect on TDP-43-transfected SH-SY5Y cells that is related to reductions in TDP-43 expression and mitochondrial damage and alleviation of oxidative stress.

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