Abstract:
: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.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Yang B,Bai Y,Yin C,Qian H,Xing G,Wang S,Li F,Bian J,Aschner M,Lu Rdoi
10.1007/s00204-018-2208-xsubject
Has Abstractpub_date
2018-06-01 00:00:00pages
2093-2108issue
6eissn
0340-5761issn
1432-0738pii
10.1007/s00204-018-2208-xjournal_volume
92pub_type
杂志文章abstract::Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and S...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-2106-7
更新日期:2018-02-01 00:00:00
abstract::Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic dr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02454-1
更新日期:2019-06-01 00:00:00
abstract::Rats were exposed to black tea (2.5% w/v) as their sole drinking liquid for either 1 day or 1 month, while controls were maintained on water. After this treatment period, all animals received a single oral dose IQ (2-amino-3-methylimidazo-[4,5-f]quinoline), and urine was collected for 48 h. Mutagenic activity of the u...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-004-0562-3
更新日期:2004-08-01 00:00:00
abstract::Perfluorocarboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA) are environmental pollutants showing high accumulation, thermochemical stability and hepatocarcinogenicity. Peroxisome proliferator-activated receptor α is suggested to mediate their toxicities, but the precise mechanism remains unclear. Previou...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-016-1888-3
更新日期:2017-06-01 00:00:00
abstract::The protective effects of various chelating agents such as D-penicillamine (D-PEN), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane sulphonate (DMPS), and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), on the renal damage induced by gold sodium thiomalate (AuTM) in rats were studied. Rats were in...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01973712
更新日期:1991-01-01 00:00:00
abstract::Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. Accordingly, there is a need for more predictive tools to assess hepatotoxicity risk in drug discovery. Three-dimensional (3D) spheroid hepatic cultures have emerged as pr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-2002-1
更新日期:2017-08-01 00:00:00
abstract::Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation couple...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-015-1582-x
更新日期:2015-12-01 00:00:00
abstract::The OECD has developed an "enhanced Test Guideline 407" (TG 407) protocol for detecting endocrine effects during the course of a 28-day testing scheme. This protocol has gone through a validation process with (anti)estrogenic and (anti)androgenic compounds and substances that affect the thyroid (thyroxine and propylth...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-004-0644-2
更新日期:2005-07-01 00:00:00
abstract::Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune d...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-018-2283-z
更新日期:2018-10-01 00:00:00
abstract::Tea (Camellia sinensis, Theaceace), a popular beverage consumed world-wide, has been studied for its preventive effects against cancer as well as cardiovascular, neurodegenerative, and other diseases. Most of the proposed beneficial effects have been attributed to the polyphenolic compounds in tea, but the nature of t...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-008-0372-0
更新日期:2009-01-01 00:00:00
abstract::Inhibition mechanism(s) of protein kinase B/Akt1 and its consequences on related cell signaling were investigated in human neuroblastoma SH-SY5Y cells exposed to 4-hydroxy-trans-2-nonenal (4-HNE), one of the most reactive aldehyde by-products of lipid peroxidation. In silico data indicate that 4-HNE interacts with kin...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1260-4
更新日期:2015-02-01 00:00:00
abstract::Although polybrominated naphthalenes (PBNs) are contaminants of the commercial fire retardant fireMaster BP-6, the individual PBN isomers have not been identified. In order to study PBNs possessing an analogous level of bromination to those found in fireMaster BP-6, three synthetic PBN mixtures, averaging 5.0, 5.3, an...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00346051
更新日期:1984-07-01 00:00:00
abstract::Chronic exposure to carbon disulfide (CS2) can induce polyneuropathy in occupational worker and experimental animals, but underlying mechanism for CS2 neurotoxicity is currently unknown. In the present study, male Wistar rats were randomly divided into two experimental groups and one control group. The rats in two exp...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-008-0399-2
更新日期:2009-06-01 00:00:00
abstract::Carbon tetrachloride (CCl4) caused a dose-dependent increase in urinary taurine which correlated with both the histological and biochemical assessment of liver damage. The peak elevation in urinary taurine occurred within the first 48 h after dosing but there was still significant taurinuria 72 and 96 h after the inte...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01973715
更新日期:1991-01-01 00:00:00
abstract::Changes in the urinary excretion of hippuric acid (HIA) and phenaceturic acid (PUA) as well as their metabolic precursors, i.e. benzoic (BA) and phenylacetic acid (PAA), in rats housed in glass metabolic cages for 4 days were monitored using gas-liquid chromatography. The amount of HIA excreted was 128 +/- 63 mumol/kg...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00324554
更新日期:1987-01-01 00:00:00
abstract::A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the rep...
journal_title:Archives of toxicology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s002040050581
更新日期:1999-02-01 00:00:00
abstract::Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, inc...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01974690
更新日期:1990-01-01 00:00:00
abstract::3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050102
更新日期:1994-01-01 00:00:00
abstract::Increasing evidence suggests that free radical-mediated oxidation of biological substrates is a key feature of Alzheimer's disease (AD) pathogenesis. While it has long been established that biomarkers of lipid peroxidation (LPO) are elevated in AD brain as well as ventricular CSF postmortem, more recent studies have d...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-015-1517-6
更新日期:2015-07-01 00:00:00
abstract::A wide variety of immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals has been documented. In contrast, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans after occupational or accidental exposu...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050072
更新日期:1994-01-01 00:00:00
abstract::Many carcinogens and mutagens are electrophilic in nature and will react with nucleophilic sites in protein and nucleic acid. Determination of the extent of formation of these adducts of genotoxic agents with protein provides a practical method of monitoring human exposure and of determining the possible risk associat...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00296978
更新日期:1987-01-01 00:00:00
abstract::As part of a study on cadmium nephrotoxicity, we studied the effect of cadmium chloride (CdCl2) in isolated human renal proximal tubules metabolizing the physiological substrate lactate. Dose-effect experiments showed that 10-500 μM CdCl2 reduced lactate removal, glucose production and the cellular levels of ATP, coen...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-010-0633-6
更新日期:2011-09-01 00:00:00
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
doi:10.1007/s00204-017-2090-y
更新日期:2018-02-01 00:00:00
abstract::Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The pre...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-1998-6
更新日期:2017-09-01 00:00:00
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
doi:10.1007/s00204-003-0503-6
更新日期:2004-01-01 00:00:00
abstract::Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is a toxic and non-essential metal. Two metal transporters, divalent metal transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for Fe transport in mammals. Here, we studied the effect of dietary Fe on the expression ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-006-0160-7
更新日期:2007-05-01 00:00:00
abstract::Mycotoxins are the most frequently occurring natural contaminants in human and animal diet. Among them, deoxynivalenol (DON), produced by Fusarium, is one of the most prevalent and thus represents an important health risk. Recent detection methods revealed new mycotoxins and new molecules derivated from the "native" m...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-016-1826-4
更新日期:2016-12-01 00:00:00
abstract::The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated le...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00317980
更新日期:1983-01-01 00:00:00
abstract::Steatosis, also known as fatty liver disease (FLD), is a disorder in which the lipid metabolism of the liver is disturbed, leading to the abnormal retention of lipids in hepatocytes. FLD can be induced by several drugs, and although it is mostly asymptomatic, it can lead to steatohepatitis, which is associated with li...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-015-1483-z
更新日期:2016-03-01 00:00:00
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
doi:10.1007/s002040050352
更新日期:1996-01-01 00:00:00