Abstract：
:Conventional in vitro toxicity studies have focused on identifying IC50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain understudied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organization) and biomechanical (Young's modulus, force of adhesion, tether force, membrane tension, tether radius) aspects of human fetal brain-derived neural progenitor cells (NPCs) induced by four classes of widely used toxic compounds, including rotenone, digoxin, N-arachidonoylethanolamide (AEA), and chlorpyrifos, under exposure up to 36 h. The sub-cellular mechanisms (apoptosis, mitochondria membrane potential, DNA damage, glutathione levels) by which these toxicants induced biochemical changes in NPCs were assessed. Results suggest a significant compromise in cell viability with increasing toxicant concentration (p < 0.01), and biophysical and biomechanical characteristics with increasing exposure time (p < 0.01) as well as toxicant concentration (p < 0.01). Impairment of mitochondrial membrane potential appears to be the most sensitive mechanism of neurotoxicity for rotenone, AEA and chlorpyrifos exposure, but compromise in plasma membrane integrity for digoxin exposure. The surviving NPCs remarkably retained stemness (SOX2 expression) even at high toxicant concentrations. A negative linear correlation (R2 = 0.92) exists between the elastic modulus of surviving cells and the number of living cells in that environment. We propose that even subtle compromise in cell mechanics could serve as a crucial marker of developmental neurotoxicity (mechanotoxicology) and therefore should be included as part of toxicology assessment repertoire to characterize as well as predict developmental outcomes.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Mahajan G,Lee MY,Kothapalli Cdoi
10.1007/s00204-019-02549-9subject
Has Abstractpub_date
2019-10-01 00:00:00pages
2979-2992issue
10eissn
0340-5761issn
1432-0738pii
10.1007/s00204-019-02549-9journal_volume
93pub_type
杂志文章abstract：:Between 0.25-25 micrograms of an aqueous solution of either mercuric chloride or methyl mercuric acetate was injected directly into the sciatic nerve of 28 adult Wistar rats. The resultant pathological changes in the nerve were examined by teasing individual fibres and by light and electron microscopy. In most respect...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00310442
更新日期：1980-12-01 00:00:00
abstract：:The uptake, distribution, and elimination of 3H-toluene in various tissues of rats were studied after inhalation or after gastric intubation. The maximum radioactivity was measured 2--3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h. After inhala...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00293651
更新日期：1977-09-28 00:00:00
abstract：:The effects of small repeated oral doses of mono-2-cresyl diphenyl phosphate (MOCP, 2.5 mg/kg/day) on hen brain and spinal cord neurotoxic esterase (NTE) were measured. The enzyme levels were depressed to about 40% and 55% of normal respectively and maintained at that level for 8 weeks. No clinical and only doubtful h...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00293807
更新日期：1980-10-01 00:00:00
abstract：:Contents of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of 16 further congeners--polychlorinated dibenzodioxins and dibenzofuranes (PCDD/PCDF)--were determined in lipids of adipose tissue and of livers of 3 stillborns and of 17 infants (0.43-44 weeks old) who died from sudden infant death syndrome. International to...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050402
更新日期：1997-01-01 00:00:00
abstract：:Whether pregnancy-induced immunosuppression when combined with exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) could exacerbate immunotoxicity has not been previously investigated. The current study evaluated the immune status of C57BL/6 pregnant and virgin mice following exposure to TCDD. To this end, syngene...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0538-8
更新日期：2004-05-01 00:00:00
abstract：:We recently reported that doxorubicin decreased the expression of calpain-1/2, while inhibition of calpain activity promoted doxorubicin-induced cardiac injury in mice. In this study, we investigated whether and how elevation of calpain-2 could affect doxorubicin-triggered cardiac injury. Transgenic mice with inducibl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02405-w
更新日期：2019-04-01 00:00:00
abstract：:The mycotoxin ochratoxin A (OTA) and its metabolite ochratoxin alpha (OT-alpha) were investigated, to examine their potency to induce sister chromatid exchanges (SCE) in cultured porcine urinary bladder epithelial cells (PUBEC) (primary culture). Serum-free cultured PUBEC were incubated for 5 h with either OTA or OT-a...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050171
更新日期：1995-01-01 00:00:00
abstract：:Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secreto...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040000174
更新日期：2000-12-01 00:00:00
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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
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-008-0288-8
更新日期：2008-10-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02342509
更新日期：1992-01-01 00:00:00
abstract：:Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-018-2170-7
更新日期：2018-04-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/BF00316365
更新日期：1989-01-01 00:00:00
abstract：:The effects of six iv infusions of an emulsion containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) on the liver and testes were investigated in 40-day-old rats. Groups of five to six animals received the emulsion every other day in doses of 0, 5, 50 or 500 mg DEHP/kg body weight. Liver effects were studied by...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00348313
更新日期：1985-12-01 00:00:00
abstract：:Tributyltin (TBT) has been shown to disrupt the ability of natural killer (NK) cells to destroy tumor targets in vitro even at exposures of 25 nM for 24 h, but cell viability was not significantly impacted. Thus, evaluation of intracellular molecular events that regulate cell viability in TBT exposed NK cells are of i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0155-4
更新日期：2007-04-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is known to influence vitamin A homeostasis. In order to investigate the mechanism behind this retinoid disruption, male Sprague-Dawley rats were exposed to TCDD at doses ranging from 0.1 to 100 micro g/kg body weight, and were killed 3 days after exposure. Additional groups...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0457-8
更新日期：2003-07-01 00:00:00
abstract：:N-methyl-D-aspartate (NMDA) and non-NMDA receptors were found to be involved in development of functional disorders caused by hexachlorophene. In order to specify the role of glutamate receptors we studied the protective effects of the selective antagonist of the kainate/(+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050011
更新日期：2000-01-01 00:00:00
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
doi：10.1007/s00204-006-0078-0
更新日期：2006-09-01 00:00:00
abstract：:Effect of repeated oral administration of hexachlorocyclohexane (HCH; 10 and 20 mg/kg body weight per day for 7, 15 and 30 days) on antioxidant defence system and lipid peroxidation (LPX) in the testis was compared between immature (15-day-old) and mature (90-day-old) rats. In both age-groups of rats, the pesticide el...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050593
更新日期：1999-03-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1865-x
更新日期：2017-05-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-010-0544-6
更新日期：2010-07-01 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：:The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02662-0
更新日期：2020-03-01 00:00:00
abstract：:The cholestatic effect of the newly developed oestradiol sulphamate (J995) was compared with that of the natural oestrogen oestradiol (E) and of the cholestatic standard oestrogen ethinyloestradiol (EE). Female ovariectomized rats were orally treated for 7 days with oestrogen doses molar equivalent to 0.01, 0.1, 1, an...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050409
更新日期：1997-01-01 00:00:00
abstract：:The uncertainties that surround the methods used for risk assessment of exposure to carcinogens have been highlighted by a recent document advocating an approach based on the T25 dose (the dose giving a 25% incidence of cancer in an appropriately designed animal experiment). This method relies on derivation of the T25...
journal_title：Archives of toxicology
pub_type：
doi：10.1007/s002040100271
更新日期：2001-11-01 00:00:00
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
doi：10.1007/s002040050223
更新日期：1995-01-01 00:00:00
abstract：:Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and de...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-015-1633-3
更新日期：2015-12-01 00:00:00
abstract：:The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral ...
journal_title：Archives of toxicology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF01974396
更新日期：1990-01-01 00:00:00
abstract：:Quantitative structure-activity relationships (QSAR) have suggested the importance of hydrogen bonding in relation to activation of the sensory irritant receptor by nonreactive volatile organic chemicals. To investigate this possibility further, three model compounds with different hydrogen bond acidity, trifluoroetha...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050281
更新日期：1996-01-01 00:00:00
abstract：:This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a sh...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0255-9
更新日期：2008-06-01 00:00:00
