Abstract:
:Chloropicrin is an aliphatic volatile nitrate compound that is mainly used as a pesticide. It has several toxic effects in animals and can cause irritating and other health problems in exposed humans. Since the mode of chloropicrin action is poorly understood, the aim of this study was to investigate molecular responses underlying chloropicrin toxicity. We used human retinal pigment epithelial cells (ARPE-19) as a model cell type because the eyes are one of the main target organs affected by chloropicrin exposure. Transmission electron microscopy images revealed that exposure to a chloropicrin concentration that decreased cell viability by 50%, evoked the formation of numerous electron-lucent, non-autophagy vacuoles in the cytoplasm with dilatation of the endoplasmic reticulum (ER). Lower concentrations led to the appearance of more electron-dense vacuoles, which contained cytoplasmic material and were surrounded by a membrane resembling autophagy vacuoles. According to immunoblotting analyses chloropicrin increased the amount of the ER-stress related proteins, Bip (about 3-fold compared to the controls), IRE1α (2.5-fold) and Gadd 153/Chop (2.5-fold), evidence for accumulation of misfolded proteins in the ER. This property was further confirmed by the increase of reactive oxygen species (ROS) production (2-2.5-fold), induction of heme oxygenase-1 (about 6-fold), and increase in the level of the tumour suppressor protein p53 (2-fold). Thus, the cytotoxicity of chloropicrin in the retinal pigment epithelium is postulated to be associated with oxidative stress and perturbation of the ER functions, which are possibly among the mechanisms involved in oculotoxicity of chloropicrin.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Pesonen M,Pasanen M,Loikkanen J,Naukkarinen A,Hemmilä M,Seulanto H,Kuitunen T,Vähäkangas Kdoi
10.1016/j.toxlet.2012.04.002subject
Has Abstractpub_date
2012-06-20 00:00:00pages
239-45issue
3eissn
0378-4274issn
1879-3169pii
S0378-4274(12)00913-7journal_volume
211pub_type
杂志文章abstract::Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and applicat...
journal_title:Toxicology letters
pub_type: 杂志文章,meta分析
doi:10.1016/j.toxlet.2019.10.021
更新日期:2020-02-01 00:00:00
abstract::Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, w...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.07.017
更新日期:2006-02-20 00:00:00
abstract::The industrial solvent dioxane (1,4-diethylene dioxide) was evaluated for teratogenic potential in Sprague-Dawley rats. The compound was administered on days 6-15 of gestation by gavage (0, 0.25, 0.5 and 1.0 ml/kg/day). A slight maternal toxicity, as evidenced by reduced weight gain, was observed with 1.0 ml/kg. Anima...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90189-4
更新日期:1985-07-01 00:00:00
abstract::Several perfluoroalkyl compounds (PFCs) are ubiquitous environmental contaminants that can biomagnify in species at high trophic levels including wild birds. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have been detected in wild birds and are known to reduce hatching success of laboratory-expose...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.07.004
更新日期:2009-10-28 00:00:00
abstract::Work with sub-natural levels of deuterium (D) in animals has demonstrated an anti-cancer effect of low D-concentration in water. Our objective was to investigate whether deuterium-depleted water (DDW) can overturn reverse manganese (Mn)-induced reduction in life span, using the Caenorhabditis elegans (C. elegans) as a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.04.014
更新日期:2012-06-20 00:00:00
abstract::The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzymes, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encoded by separate genes. Common functional polymorphisms of the transcribed region are known for ...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(99)00214-3
更新日期:2000-03-15 00:00:00
abstract::Cadmium-binding proteins (CdBPs) in the cytosol fractions from several organs of man orally exposed to cadmium (Cd) were examined by gel chromatography. In kidney and liver most of the cadmium (76-87%) in the cytosols was bound to metallothionein, and hepatic metallothionein contained zinc also at a similar level. The...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90160-6
更新日期:1982-05-01 00:00:00
abstract::Heptachlor is a major component of the insecticide, chlordane. It is a health hazard but is still in use in some countries of Southeast Asia. To elucidate the toxicity of heptachlor its effects on mice after oral and intraperitoneal administration were studied. A 3-day group, 92-day group and 180-day group were given ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90054-p
更新日期:1990-11-01 00:00:00
abstract::Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expres...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.10.024
更新日期:2006-06-01 00:00:00
abstract::There have been many concerns about the possible adverse effects of thyroid hormone-disrupting chemicals in the environment. Because thyroid hormones are essential for regulating the growth and differentiation of many tissues, disruption of thyroid hormones during the neonatal period of an organism might lead to perma...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.01.005
更新日期:2018-04-01 00:00:00
abstract::Effects of sublethal concentration (0.8 of LC50 96 h) of nickel sulphate (NiSO4 X 7H2O) on muscle glycogen and blood lactic acid levels of a freshwater teleost, Colisa fasciatus, at time intervals from 3-96 h have been recorded. Muscle glycogen levels showed a general decrease at all time intervals compared with contr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90193-0
更新日期:1984-01-01 00:00:00
abstract::To determine whether occupational exposure to trichloroethylene (TCE) influences sympathetic nerve activity, serum dopamine-beta-hydroxylase (DBH) activities were analyzed in 84 male workers exposed to TCE and 83 male age-matched controls. The workers were exposed to about 22 ppm TCE in air. There were no significant ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90187-q
更新日期:1990-12-01 00:00:00
abstract::A computer program (Q-test) was used to evaluate the combined toxic effects of nerve agent GF and its combined form with sarin (GB/GF) in mice. Efficacy of Jielin Injection, the 2-PAM-containing antidote used successfully in China for the treatment of organophosphate pesticide poisoning, was also evaluated and compare...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(97)00057-x
更新日期:1997-08-22 00:00:00
abstract::The incidence of spontaneous neoplasms in outbred, inbred and F1 hybrid strains was compared using the Charles River-CD rat and mouse, the F344 rat, and B6C3HF1 mouse. These strains are commonly used in carcinogenic studies. Each strain has a consistent pattern of tumor occurrence; testicular, pituitary and lymphoreti...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90113-8
更新日期:1982-04-01 00:00:00
abstract::The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antid...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.03.007
更新日期:2018-09-01 00:00:00
abstract::This paper compares two methods for global optimization of physiologically based toxicokinetic models: Monte Carlo optimization, which searches randomly for the optimum; and the simplex method, which updates systematically an array of parameter values. Two measures of goodness-of-fit are also contrasted: criterion fun...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90103-5
更新日期:1993-08-01 00:00:00
abstract::Pneumotoxicity of butylated hydroxytoluene (BHT) applied to the skin of CD-1 mice was investigated and compared with that of butylated hydroxyanisole (BHA). To 6 groups of 10 male mice and 10 female mice 0.1 ml of dimethylsulfoxide (DMSO) solutions containing 0, 5, 10, 20, or 30 mg of BHT or 30 mg of BHA were topicall...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90151-7
更新日期:1986-11-01 00:00:00
abstract::The lethal effects of d-amphetamine and phencyclidine (PCP) were compared when adult male mice were placed into isolated or aggregated (12 mice/cage) conditions. The LD50 of d-amphetamine decreased approx. 30-fold between isolated (87.9 mg/kg) and aggregated (2.8 mg/kg) conditions. In contrast, PCP showed only a 1.3-f...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90181-3
更新日期:1982-07-01 00:00:00
abstract::There are multiple lines of evidence showing that environmental toxicants including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a phenylpyrazole insecticide that acts on insect GABA receptors. Although the action of FPN is restricted to insect neuronal or muscular transmitter systems, a few stu...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.02.022
更新日期:2012-05-20 00:00:00
abstract::The toxicity of methylmercury is sufficiently high to justify an evaluation of the risk from the consumption of contaminated food. In the method of risk assessment proposed here, distribution frequencies are assigned to the parameters in question, rather than mean values. Total body burden is estimated by numerical si...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90080-7
更新日期:1982-02-01 00:00:00
abstract::(1) The hypothesis that inhalational anesthetics affect G-protein linked alpha2 adrenergic signaling pathway was investigated using human platelets as a model system. (2) Alpha2 receptor stimulation by UK-14304, a potent and selective agonist, inhibits cAMP production induced by prostaglandin I2 (PGI2). (3) Brief stim...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00174-x
更新日期:1998-11-23 00:00:00
abstract::Benzodiazepines have wide-spread used in pharmacotherapy for their anxiolytic, myorelaxant, hypnotic, amnesic and anticonvulsive properties. Despite benzodiazepines are used in clinics over 50 years, they have not been surprisingly tested for capability to induce major drug-metabolizing cytochromes P450. In the curren...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.01.004
更新日期:2010-03-15 00:00:00
abstract::A previous study revealed that a single i.p. administration of 6 mg/kg body wt. of mercuric chloride (MC) durably inhibits the rat cerebral microvascular Na+/K(+)-ATPase activity [1]. In this study, cerebral microvessels isolated 18 h after MC treatment were compared to those obtained from control rats and subsequentl...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90127-9
更新日期:1994-02-15 00:00:00
abstract::Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days sub...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90141-9
更新日期:1985-01-01 00:00:00
abstract::Previous studies have suggested that elevated blood homocysteic acid (HCA) levels increased the risk of Alzheimer's disease (AD), but the underlying mechanisms are unclear. Herein, we studied the neuronal toxicity of HCA and the underlying mechanisms in HT-22 cells. Results showed that HCA induced cell death in concen...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.08.011
更新日期:2013-10-23 00:00:00
abstract::Colistin is a polypeptide antibiotic that effectively treats infections caused by multidrug-resistant Gram-negative bacteria, but its clinical use is limited due to nephrotoxicity. The purpose of the present study was to identify biomarkers of colistin-induced nephrotoxicity and to further characterize the mechanisms ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.02.018
更新日期:2016-04-25 00:00:00
abstract::The HER2 pathway plays a pivotal role in cell proliferation and differentiation, while the receptor overexpression caused by amplification of HER2 gene is associated with the growth of several tumors. Previously published clinical trials have demonstrated that antibody-conjugated drugs (ADCs) remarkably improved clini...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.12.027
更新日期:2020-05-15 00:00:00
abstract::Male mice (Q strain) received a single i.p. injection of 14 organophosphorus compounds, including 11 insecticides, administered on separate occasions. After a recovery period of 10 to 15 days, the cytogenic effects were analyzed in primary spermatocytes at diakinesis-metaphase I corresponding to the treatment of A4-B ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90090-0
更新日期:1984-06-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a proven animal carcinogen. Occupational cohorts with the highest exposures imply that there is a small risk of all cancers combined, but it is difficult to pinpoint the confounding effect of the main chemicals. Studies after major accidents do not unequivocally confirm th...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2012.02.007
更新日期:2012-05-05 00:00:00
abstract::The dose-response curve obtained in toxicity testing is a mirror image of the susceptibility distribution in the treated population, i.e. it follows increasing tolerance of the individuals to the adverse effects of the chemical under investigation. Defining a dose as a maximum tolerated exposure level, therefore, spli...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(01)00458-1
更新日期:2002-02-07 00:00:00