Activation of autophagic flux and the Nrf2/ARE signaling pathway by hydrogen sulfide protects against acrylonitrile-induced neurotoxicity in primary rat astrocytes.


:Hydrogen sulfide (H2S), the third gasotransmitter, has been shown to act as a neuroprotective factor in numerous pathological processes; however, its underlying mechanism(s) of action remain unclear. It is widely accepted that activation of moderate autophagy and the Nrf2/ARE signaling pathway play important roles in the biological self-defense systems. In the present study, we investigated whether exogenous H2S protects against the cytotoxicity of acrylonitrile (AN), a neurotoxin, in primary rat astrocytes. We found that pretreatment for 1 h with sodium hydrosulfide (NaHS), a donor of H2S (200-800 µM), significantly attenuated the AN-induced decrease in cell viability, increase in lactate dehydrogenase release and morphological changes. Furthermore, NaHS significantly attenuated AN-induced oxidative stress by reducing reactive oxygen species (ROS) levels and increasing glutathione (GSH) concentration. Moreover, NaHS activated the autophagic flux, detectable as a change in autophagy-related proteins (Beclin-1, Atg5 and p62), the formation of acidic vesicular organelles and LC3B aggregation, confirmed by adenoviral expression of mRFP-GFP-LC3. Additionally, NaHS stimulated translocation of Nrf2 into the nucleus and increased expression of heme oxygenase-1 and γ-glutamylcysteine synthetase, downstream targets of Nrf2. Notably, the autophagy inhibitor 3-methyladenine and Beclin-1, or Nrf2-targeted siRNA, significantly attenuated the neuroprotective effects of NaHS against AN-induced neurotoxicity. In conclusion, we identified a crucial role of  autophagy and the Nrf2/ARE signaling pathway in H2S-mediated neuroprotection against AN-induced toxicity in primary rat astrocytes. Our findings provide novel insights into the mechanisms of H2S-mediated neuroprotection, and suggest that H2S-based donors may serve as potential new candidate drugs to treat AN-induced neurotoxicity.


Arch Toxicol


Archives of toxicology


Yang B,Bai Y,Yin C,Qian H,Xing G,Wang S,Li F,Bian J,Aschner M,Lu R




Has Abstract


2018-06-01 00:00:00














  • Histopathologic effects of maternal 4-tert-octylphenol exposure on liver, kidney and spleen of rats at adulthood.

    abstract::The present study was performed to investigate the potential toxic effects of prenatal exposure to 4-tert-octylphenol (OP) on liver, kidney, spleen, and hematologic parameters of male and female rats in adult life. The rats were treated with OP subcutaneously in utero at doses of control (vehicle, corn oil), 100 or 25...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Barlas N,Aydoğan M

    更新日期:2009-04-01 00:00:00

  • Activation of sterol regulatory element-binding proteins in mice exposed to perfluorooctanoic acid for 28 days.

    abstract::Perfluoroalkyl acids are widely used in numerous industrial and commercial applications due to their unique physical and chemical characteristics. Although perfluorooctanoic acid (PFOA) is associated with hepatomegaly through peroxisome proliferator-activated receptor α (PPARα) activation, liver fat accumulation and c...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Yan S,Wang J,Dai J

    更新日期:2015-09-01 00:00:00

  • Novel insights into renal D-amino acid oxidase accumulation: propiverine changes DAAO localization and peroxisomal size in vivo.

    abstract::Chronic exposure to propiverine, a frequently prescribed pharmaceutical for treatment of overactive bladder and incontinence, provokes massive protein accumulation in the cytosol and nucleus of renal proximal tubule epithelial cells in rats. Previously, the accumulating protein was identified as D-amino acid oxidase (...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Luks L,Sacchi S,Pollegioni L,Dietrich DR

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  • Mechanisms and in vitro models of drug-induced cholestasis.

    abstract::Cholestasis underlies one of the major manifestations of drug-induced liver injury. Drug-induced cholestatic liver toxicity is a complex process, as it can be triggered by a variety of factors that induce 2 types of biological responses, namely a deteriorative response, caused by bile acid accumulation, and an adaptiv...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审


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  • Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

    abstract::In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. P...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审


    authors: Zhang B,Huang K,Zhu L,Luo Y,Xu W

    更新日期:2017-07-01 00:00:00

  • Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin.

    abstract::As previously demonstrated, chronic administration of phenobarbital (0.05% in the drinking water) and of nafenopin (0.1% in the diet) increases the incidence and the kinetics of appearance of liver cancers. If bile acids play a key role in liver carcinogenesis, it might thus be expected that treatments like phenobarbi...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:1994-01-01 00:00:00

  • Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice.

    abstract::Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron i...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:1996-01-01 00:00:00

  • Use of the dog as non-rodent test species in the safety testing schedule associated with the registration of crop and plant protection products (pesticides): present status.

    abstract::The results from a survey of the expert information that is publicly accessible on the use of the dog as test species during the regulatory evaluation of agricultural chemicals and pesticides are reported. Methods that are being used or considered in order to reduce the number of dogs used for this purpose are describ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:2005-11-01 00:00:00

  • Response to Uptake of microplastics and related health effects: a critical discussion of Deng et al., Scientific reports 7: 46687, 2017.

    abstract:: ...

    journal_title:Archives of toxicology

    pub_type: 评论,信件


    authors: Deng Y,Zhang Y

    更新日期:2019-01-01 00:00:00

  • Toxicity of PCB-126 in European flounder (Platichthys flesus) with emphasis on histopathology and cytochrome P4501A induction in several organ systems.

    abstract::A series of experiments was set up to elucidate the effects of pollution on marine and estuarine fish health, since the European flounder (Platichthys flesus) has shown a relatively high prevalence of (pre)neoplastic liver lesions and lymphocystis virus disease in Dutch coastal and estuarine waters. The hypothesis of ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:2001-04-01 00:00:00

  • Possible role of the acetone-inducible cytochrome P-450IIE1 in the metabolism and hepatotoxicity of thiobenzamide.

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    journal_title:Archives of toxicology

    pub_type: 杂志文章


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  • The protective role of NAD(P)H:quinone oxidoreductase 1 on acetaminophen-induced liver injury is associated with prevention of adenosine triphosphate depletion and improvement of mitochondrial dysfunction.

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    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hwang JH,Kim YH,Noh JR,Gang GT,Kim KS,Chung HK,Tadi S,Yim YH,Shong M,Lee CH

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  • Extracellular nucleic acid scavenging rescues rats from sulfur mustard analog-induced lung injury and mortality.

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    journal_title:Archives of toxicology

    pub_type: 杂志文章


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  • Characterization of the role played by antigen challenge in the suppression of in vivo humoral immunity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    abstract::The goal of these studies was to characterize the role played by antigen challenge in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunosuppression. The effects of single exposure to TCDD (4.2, 14, and 42 microg/kg) in B6C3F1 mice on the reverse plaque assay (RPA; no sensitization) and the sheep red blood cell ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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  • Use of M-mode and Doppler echocardiography to investigate the cardiotoxicity of minoxidil in beagle dogs.

    abstract::Doppler and M-mode echocardiography (EC) were used to investigate the effects of minoxidil on the cardiac function of the dog and potentially to clarify the pathogenesis of cardiac lesions, in particular the necrotic lesion in the left ventricle and the haemorrhagic lesion in the right atrium. Groups of three dogs wer...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Hanton G,Gautier M,Bonnet P

    更新日期:2004-01-01 00:00:00

  • The role of epoxide hydrolases in health and disease.

    abstract::Epoxide hydrolases (EH) are ubiquitously expressed in all living organisms and in almost all organs and tissues. They are mainly subdivided into microsomal and soluble EH and catalyze the hydration of epoxides, three-membered-cyclic ethers, to their corresponding dihydrodiols. Owning to the high chemical reactivity of...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审


    authors: El-Sherbeni AA,El-Kadi AO

    更新日期:2014-11-01 00:00:00

  • 3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo.

    abstract::Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a poten...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:2018-10-01 00:00:00

  • Effect of bolesatine on phospholipid/calcium dependent protein kinase in Vero cells and in rat thymus.

    abstract::Bolesatine, a glycoprotein from Boletus satanas Lenz, has previously been shown to be mitogenic to rat and human lymphocytes at very low concentrations, whereas higher concentrations inhibit protein synthesis in vitro and in several in vivo systems. The mechanism whereby this mitogenic activity occurs was previously u...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:1995-01-01 00:00:00

  • Effect of ziram on natural killer, lymphokine-activated killer, and cytotoxic T lymphocyte activity.

    abstract::Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031-4 μM in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytoto...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:2012-03-01 00:00:00

  • Role of biological antioxidants in benzanthrone toxicity.

    abstract::Previous studies indicate that benzanthrone, an anthraquinone dye intermediate, caused significant depletion of ascorbic acid (AsA). In this investigation the effect of benzanthrone on the status of different forms of AsA and other bio-antioxidants such as glutathione (GSH) was studied. Oral administration of benzanth...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Dwivedi N,Das M,Khanna SK

    更新日期:2001-06-01 00:00:00

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    abstract::Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of er...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:1996-01-01 00:00:00

  • A direct involvement of the central nervous system in hypophagia and inhibition of respiratory rate in rats after treatment with O,O,S-trimethyl phosphorothioate.

    abstract::O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous syste...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ohtaka K,Hamade N,Yamazaki Y,Suzuki M,Koizumi A

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  • Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans.

    abstract::Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related prec...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Yu D,Wu L,Gill P,Tolleson WH,Chen S,Sun J,Knox B,Jin Y,Xiao W,Hong H,Wang Y,Ren Z,Guo L,Mei N,Guo Y,Yang X,Shi L,Chen Y,Zeng L,Dreval K,Tryndyak V,Pogribny I,Fang H,Shi T,McCullough S,Bhattacharyya S,S

    更新日期:2018-02-01 00:00:00

  • Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish.

    abstract::We previously reported a novel toxic peptide identified from the anthozoan Protopalythoa variabilis transcriptome which is homologous to a novel structural type of sodium channel toxin isolated from a parental species (Palythoa caribaeorum). The peptide was named, according to its homologous, as Pp V-shape α-helical p...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Liao Q,Li S,Siu SWI,Morlighem JRL,Wong CTT,Wang X,Rádis-Baptista G,Lee SM

    更新日期:2019-01-01 00:00:00

  • Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure.

    abstract::The effect of intracerebroventricular (i.c.v.) administration of cadmium or magnesium on central calcium-dependent blood pressure regulation was investigated. The systolic blood pressure of spontaneously hypertensive rats (SHR; male, 13 weeks of age) decreased following i.c.v. administration of cadmium chloride (20 nm...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Sutoo D,Akiyama K

    更新日期:2000-03-01 00:00:00

  • In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands.

    abstract::In the present study the toxicological potential of a tumor-inhibiting dinuclear platinum(II) complex (bis(acetato)diammine-bis-micro-acetato diplatinum(II) dihydrate (BAP)) was evaluated, utilizing in vitro models of nephrotoxicity, myelosuppression and neurotoxicity. Regarding the discrepancies between the hallmark ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Momekov G,Ferdinandov D,Bakalova A,Zaharieva M,Konstantinov S,Karaivanova M

    更新日期:2006-09-01 00:00:00

  • Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells.

    abstract::The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1, 5 and 10 microM, DZO did not cause cell death but it impaired the outgrowth of...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


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  • A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population.

    abstract::MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G>C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigat...

    journal_title:Archives of toxicology

    pub_type: 杂志文章


    authors: Ma L,Zhu L,Gu D,Chu H,Tong N,Chen J,Zhang Z,Wang M

    更新日期:2013-05-01 00:00:00

  • Cytotoxicity of cyclophosphamide, paclitaxel, and docetaxel for tumor cell lines in vitro: effects of concentration, time and cytochrome P450-catalyzed metabolism.

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    journal_title:Archives of toxicology

    pub_type: 杂志文章


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    更新日期:2000-10-01 00:00:00

  • Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance.

    abstract::The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as "vomitoxin" because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detecte...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审


    authors: Pestka JJ

    更新日期:2010-09-01 00:00:00