α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish.


:α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 μM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased heart rate. Notably, we found that α-asarone impaired the cardiac function of zebrafish by prolonging the mean QTc duration and causing T-wave abnormalities. The expressions of cardiac development-related key transcriptional regulators tbx5, nkx2.5, hand2, and gata5 were all changed under α-asarone exposure. Further investigation addressing the mechanism indicated that α-asarone triggered apoptosis mainly in the heart region of zebrafish. Moreover, the elevated expression of puma, cyto C, afap1, caspase 3, and caspase 9 in treated zebrafish suggested that mitochondrial apoptosis is likely to be the main reason for α-asarone induced cardiotoxicity. These findings revealed the cardiac developmental toxicity of α-asarone, expanding our knowledge about the toxic effect of α-asarone on living organisms.


Toxicol Lett


Toxicology letters


Shang X,Ji X,Dang J,Wang L,Sun C,Liu K,Sik A,Jin M




Has Abstract


2020-05-15 00:00:00












  • Responses of estrogen sensitive tissues in female Wistar rats to pre- and postnatal isoflavone exposure.

    abstract::Effects of isoflavones on estrogen sensitive tissues are discussed controversially. This study was designed to investigate tissue specific effects of an isoflavone exposure through different periods of life in female Wistar rats and to compare the effects of genistein (GEN) to those of mixed dietary isoflavones, GEN a...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Hertrampf T,Ledwig C,Kulling S,Molzberger A,Möller FJ,Zierau O,Vollmer G,Moors S,Degen GH,Diel P

    更新日期:2009-12-15 00:00:00

  • Effect of saccharin on the induction of chromosomal translocations in male mice and their F1 offspring.

    abstract::The dose-dependent effects of sodium saccharin on the fertility and the induction of chromosomal translocations in treated mice and their F1 males were examined. C3H X 101 mice were treated with saccharin for 2 successive weeks at doses of 200 and 500 mg/kg of body wt. Data from the fertility study showed that sacchar...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Pecevski J,Vuksanović L,Savković N,Alavantić D,Radivojević D

    更新日期:1983-12-01 00:00:00

  • Effects of ceftaroline on the innate immune and on the inflammatory responses of bronchial epithelial cells exposed to cigarette smoke.

    abstract::The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections accelerated the functional respiratory decline. The present study assessed the effects of ceftaroline on TLR2 and TLR4 and on pro-inflammatory responses in airway epithelial cells (16HBE cell line and prim...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Pace E,Ferraro M,Di Vincenzo S,Siena L,Gjomarkaj M

    更新日期:2016-09-06 00:00:00

  • The distribution of esterases in the skin of the minipig.

    abstract::Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Jewell C,Prusakiewicz JJ,Ackermann C,Payne NA,Fate G,Williams FM

    更新日期:2007-09-10 00:00:00

  • Biological monitoring of mercury vapour exposure by scalp hair analysis in comparison to blood and urine.

    abstract::The reliability of human scalp hair as an indicator of mercury vapour exposure is contentious. In this study mercury concentrations in hair were compared with those in blood and urine of 20 dental students during their first "occupational" exposure to mercury vapour. Samples were collected before, at the end of the te...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Wilhelm M,Müller F,Idel H

    更新日期:1996-11-01 00:00:00

  • Influence of hOGG1, XRCC1 and XRCC3 genotypes on biomarkers of genotoxicity in workers exposed to cobalt or hard metal dusts.

    abstract::Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. We examined whether variations in genes involved in base-excision (hOGG1, XRCC1) and double strand break (XRCC3) DNA repair contribute to inter-individual differences in genotoxic effects induced in ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Mateuca R,Aka PV,De Boeck M,Hauspie R,Kirsch-Volders M,Lison D

    更新日期:2005-04-10 00:00:00

  • Chloroacetonitrile induces oxidative stress and apoptosis in mouse fetal liver.

    abstract::Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. The present study was designed to investigate the potential adverse effects of maternal exposure to CAN on fetal liver in mice. Based on an initial dose-response experiment, CAN (25mg/(kgday)) was given orally to pregnant mice at ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Abdel-Naim AB,Nagy AA,Mohamadin AM,El-Mazar HM,Ahmed AE

    更新日期:2009-10-28 00:00:00

  • MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs.

    abstract::The antioxidant activity of genistein is associated with preventing atherosclerosis; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Zhang H,Zhao Z,Pang X,Yang J,Yu H,Zhang Y,Zhou H,Zhao J

    更新日期:2017-08-05 00:00:00

  • A comparative study of leukaemia inhibitory factor and interleukin-1alpha intracellular content in a human keratinocyte cell line after exposure to cosmetic fragrances and sodium dodecyl sulphate.

    abstract::According to European laws animal testing in cosmetic industry will be prohibited in a few years and it will be replaced by alternative methods based on cell and tissue culture. Many ingredients of cosmetic formulations are potentially causes of skin inflammation and sensibilization. Since cytotoxicity is known, among...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Parodi A,Sanguineti R,Catalano M,Penco S,Pronzato MA,Scanarotti C,Bassi AM

    更新日期:2010-02-01 00:00:00

  • Fatty acid alterations in liver and milk of cadmium exposed rats and in brain of their suckling offspring.

    abstract::Fatty acid composition was studied in milk at day 14 and in liver at day 24 after parturition of lactating rats exposed to 0 ppm, 5 ppm or 25 ppm cadmium (Cd) via drinking water for 17 days during lactation, and in the brain of their offspring at day 19 after birth. In the liver phospholipid fraction, 22:5(n-3) was si...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Grawé KP,Pickova J,Dutta PC,Oskarsson A

    更新日期:2004-03-14 00:00:00

  • Acid rain: effects on arachidonic acid metabolism in perfused and ventilated guinea-pig lung.

    abstract::Isolated, perfused and ventilated guinea-pig lungs were exposed for 10 min to acid (sulphuric + nitric acid) aerosol mimicking acid rain at pH 4.5 or 2.5, as well as to a control distilled water aerosol (pH 6.0-6.5). Lung perfusing solution was recovered and thromboxane (TX) B2 and leukotriene (LT) B4 were measured by...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Preziosi P,Ciabattoni G

    更新日期:1987-11-01 00:00:00

  • Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals.

    abstract::The aim of the current HBM-study is to further the understanding of the impact of inter- and intra-individual variability in HBM surveys as it may have implications for the design and interpretation of the study outcomes. As spot samples only provide a snapshot in time of the concentrations of chemicals in an individu...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Smolders R,Koch HM,Moos RK,Cocker J,Jones K,Warren N,Levy L,Bevan R,Hays SM,Aylward LL

    更新日期:2014-12-01 00:00:00

  • RACK-1 overexpression protects against goniothalamin-induced cell death.

    abstract::Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Over...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Inayat-Hussain SH,Wong LT,Chan KM,Rajab NF,Din LB,Harun R,Kizilors A,Saxena N,Mourtada-Maarabouni M,Farzaneh F,Williams GT

    更新日期:2009-12-15 00:00:00

  • Indirect human exposure to pharmaceuticals via drinking water.

    abstract::There are numerous observations of pharmaceuticals (or their metabolites) as contaminants in wastewater, surface water and groundwater. This implies a potential for indirect human exposure to pharmaceuticals via drinking water supplies. Various effect benchmarks may be employed in an evaluation of the significance of ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Webb S,Ternes T,Gibert M,Olejniczak K

    更新日期:2003-05-15 00:00:00

  • Protective effect of metallothionein inducing metals on lethal toxicity of cis-diamminedichloroplatinum in mice.

    abstract::A protective effect of preadministration of the metals Cu, Bi, Zn, Hg, Cd, Ni or Co, against lethal toxicity of cis-diamminedichloroplatinum (Cisplatin; CDDP) was observed in mice. However, the protective effect seems not always to correlate with metallothionein (MT) levels in the liver and kidney of mice treated with...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Naganuma A,Satoh M,Koyama Y,Imura N

    更新日期:1985-02-01 00:00:00

  • Progress in understanding adjuvant immunotoxicity mechanisms.

    abstract::Over the last twenty years research has provided an important insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of immunostimulating drugs and adjuvants. In this article we provide an update of the present knowledge relating to the various par...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Batista-Duharte A,Lindblad EB,Oviedo-Orta E

    更新日期:2011-06-10 00:00:00

  • Toxicological evaluation by in vitro and in vivo assays of an aqueous extract prepared from Echinodorus macrophyllus leaves.

    abstract::Toxicity of an aqueous extract prepared from Echinodorus macrophyllus dried leaves, a plant used in folk medicine to treat inflammation and kidney malfunctions, was estimated by different bioassays. Mutagenicity of the aqueous extract was evaluated in the Salmonella/microsome assay (TA97a, TA98, TA100 and TA102 strain...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: da Costa Lopes L,Albano F,Augusto Travassos Laranja G,Marques Alves L,Fernando Martins e Silva L,Poubel de Souza G,de Magalhães Araujo I,Firmino Nogueira-Neto J,Felzenszwalb I,Kovary K

    更新日期:2000-08-16 00:00:00

  • Effect of subchronic exposure to inorganic arsenic on the structure and function of the intestinal epithelium.

    abstract::Inorganic arsenic (As), the most toxic form of As found in water and food, is considered a human carcinogen. Numerous studies show its systemic toxicity, describing pathologies associated with chronic exposure. The main pathway of exposure to inorganic As is oral, but many of the events that occur during its passage t...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Chiocchetti GM,Vélez D,Devesa V

    更新日期:2018-04-01 00:00:00

  • Bardoxolone methyl modulates efflux transporter and detoxifying enzyme expression in cisplatin-induced kidney cell injury.

    abstract::Cisplatin is prescribed for the treatment of solid tumors and elicits toxicity to kidney tubules, which limits its clinical use. Nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2) is a critical transcription factor that has been shown to protect against kidney injury through activation of antioxidant mechanism...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Atilano-Roque A,Aleksunes LM,Joy MS

    更新日期:2016-09-30 00:00:00

  • Antagonistic effect of melatonin against cyanide-induced seizures and acute lethality in mice.

    abstract::The effect of melatonin on potassium cyanide-induced neurotoxicity was investigated in vivo. The ED50 value of potassium cyanide, as measured by induction of tonic and clonic seizures, was significantly increased by 1.5- or 1.8-fold by s.c. preinjection of melatonin (20, 100 or 345 mg/kg) in mice. The preventive effec...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Yamamoto H,Tang HW

    更新日期:1996-09-01 00:00:00

  • Increased activity of certain hepatic drug-metabolizing enzymes due to subchronic exposure to bromobenzene.

    abstract::Male Sprague-Dawley rats were treated i.p. with different doses of bromobenzene (0, 0.1, 0.2, 0.3 and 0.5 mmol/kg) in corn oil for 4 weeks. The animals were killed 24 h after the end of the treatment for hepatic drug metabolism studies. A significant induction of the activities of microsomal aniline hydroxylase (51%) ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Chakrabarti S

    更新日期:1984-01-01 00:00:00

  • Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 2: personal care product ingredients.

    abstract::An intensive study was conducted to provide data on intra- and inter-individual variation in urinary excretion of a series of ingredients in personal care products (parabens, triclosan, benzophenones) and bisphenol A (BPA, not expected to be an ingredient) in 8 volunteers over 6 days. Exposure diaries recorded use of ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Koch HM,Aylward LL,Hays SM,Smolders R,Moos RK,Cocker J,Jones K,Warren N,Levy L,Bevan R

    更新日期:2014-12-01 00:00:00

  • Rat hepatic CYP1A1 and CYP1A2 induction by menadione.

    abstract::The effects of menadione on activities and expression of cytochrome P450 (CYP) 1A subfamily (CYP1A) isozymes in rat hepatic tissue were examined. When rats were treated orally with 15 mg/kg menadione for 4 days, the elevation of hepatic CYP1A1/1A2 specific activities in microsomal preparations was detected with approx...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Sidorova YA,Grishanova AY,Lyakhovich VV

    更新日期:2005-02-15 00:00:00

  • Deregulation of NR2E3, an orphan nuclear receptor, by benzo(a)pyrene-induced oxidative stress is associated with histone modification status change of the estrogen receptor gene promoter.

    abstract::We previously reported that NR2E3, an orphan nuclear receptor, plays an important role in maintaining the basal expression of estrogen receptor α (ER) and that the NR2E3 level is highly correlated with the relapse-free survival of breast cancer patients. Here, we investigated the role of NR2E3 in benzo(a)pyrene (BaP)-...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Khanal T,Kim D,Johnson A,Choubey D,Kim K

    更新日期:2015-09-17 00:00:00

  • Lack of effect of perinatal lead exposure on kappa-opioid receptor function.

    abstract::The effects of lead exposure have been studied upon the behavioural and diuretic responses to the kappa-opioid receptor agonist U-50488H in neonatal rats. Lead was administered in the maternal drinking water (100, 300 and 1000 ppm) from conception to postnatal day 14. The hyperactivity, wall climbing behaviours and di...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Jackson HC,Kitchen I

    更新日期:1990-01-01 00:00:00

  • Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium.

    abstract::The role of intra- and extracellular calcium in the activation of human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM) were studied by using soluble, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), or particulate stimuli, quartz or chrysotile. A calciu...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Ruotsalainen M,Naarala J,Savolainen KM

    更新日期:1995-08-01 00:00:00

  • Suppressive effect of tobacco smoke extracts on oral P-glycoprotein function and its impact in smoke-induced insult to oral epidermal cells.

    abstract::P-glycoprotein (Pgp) participates in the export of numerous toxins, drugs, and physiological compounds. To examine the involvement of Pgp in smoke-induced oral cell insult, the effects of extracts of the mainstream tobacco smoke (TS) on Pgp were studied in an oral epidermal carcinoma cell line, OECM-1. TS was first ex...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Pan WC,Chen RM,Shen YC,Chen CC,Ueng YF

    更新日期:2009-03-10 00:00:00

  • Recent developments in methanol toxicity.

    abstract::The disposition of methanol and its putative toxic metabolite formate has been studied in humans, non-human primates, and rodents after exposure to high, neurotoxic doses. The rate at which rodents detoxify formate is more rapid than that of primates. Formate, an endogenous biological substrate, is detoxified by metab...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Medinsky MA,Dorman DC

    更新日期:1995-12-01 00:00:00

  • Mathematical description of the uptake of hydrocarbons in jet fuel into the stratum corneum of human volunteers.

    abstract::The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick's laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, u...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Kim D,Farthing MW,Miller CT,Nylander-French LA

    更新日期:2008-05-30 00:00:00

  • Sex-specific cytochrome P450 as a cause of sex- and species-related differences in drug toxicity.

    abstract::Male rats are the most frequently used experimental animals in drug toxicity tests. However, there are clear sex-related differences in toxicity of various drugs and chemicals in rats. These differences, in most cases, are closely connected with the sex-related differences in hepatic drug metabolisms. Recent studies i...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Kato R,Yamazoe Y

    更新日期:1992-12-01 00:00:00