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 antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating the skin, is activated by SM and 2-chloroethyl ethyl sulfide (CEES), an SM analog, in vitro, suggesting it may promote vesicant injury. Here, we investigated the effects of TRPA1 inhibitors, and an inhibitor of Calcitonin Gene Related Peptide (CGRP), a neurogenic inflammatory peptide released upon TRPA1 activation, in a CEES-induced mouse ear vesicant model (CEES-MEVM). TRPA1 inhibitors (HC-030031 and A-967079) and a CGRP inhibitor (MK-8825) reduced skin edema, pro-inflammatory cytokines (IL-1β, CXCL1/KC), MMP-9, a protease implicated in skin damage, and improved histopathological outcomes. These findings suggest that TRPA1 and neurogenic inflammation contribute to the deleterious effects of vesicants in vivo, activated either directly by alkylation, or indirectly, by reactive intermediates or pro-inflammatory mediators. TRPA1 and CGRP inhibitors represent new leads that could be considered for validation and further development in other vesicant injury models.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Achanta S,Chintagari NR,Brackmann M,Balakrishna S,Jordt SEdoi
10.1016/j.toxlet.2018.03.007subject
Has Abstractpub_date
2018-09-01 00:00:00pages
140-148eissn
0378-4274issn
1879-3169pii
S0378-4274(18)30092-4journal_volume
293pub_type
杂志文章abstract::Letimide is a new efficient analgesic salicylate derivative. In this study we evaluated its cytogenetic and teratogenic potential. For chromosomal aberrations and sister chromatid exchange analysis we tested 250, 375, 500 and 625 micrograms/ml of letimide in human lymphocyte cultures in vitro, and for the in vivo cyto...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(91)90095-n
更新日期:1991-04-01 00:00:00
abstract::Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 +/- 15.8 micrograms nitrite/h X kg body wt. was detected between 5-24 h. Cerebral glutathione concentration was below the co...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90281-3
更新日期:1983-10-01 00:00:00
abstract::Although the interest is growing towards glyoxalases and methylglyoxal, their role in metabolism is still an enigma. In this paper, the effects of methylglyoxal in both in vivo and in vitro mammalian systems are reviewed and correlated with its interaction with macromolecules (nucleic acids, proteins). The theories on...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(94)90184-8
更新日期:1994-07-01 00:00:00
abstract::Toxicity of a compound for an organism is dependent on the route of exposure, the amount (or concentration), the way in which the compound is taken up, distributes and is eliminated from the organism (ADME, kinetics) and the intrinsic properties (reactivity; mode of action, dynamics) of the compound towards the organi...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(02)00367-3
更新日期:2003-02-18 00:00:00
abstract::Two groups of C57BL/6J mice received a single oral dose of 1 nmol/kg 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) alone or in combination with 300 mumol/kg 2,2',4,4',5,5'-hexachlorobiphenyl (HxCB). The disposition of TCDD in liver, fat, skin, spleen, lung and blood was studied at days 3, 7, 13 and 34 after dosage. H...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03387-z
更新日期:1995-10-01 00:00:00
abstract::Monosodium glutamate (MSG) was administered to adult male mice for 6 d at dose levels of 2, 4 and 8 mg/g b.w. Dose levels of 4 and 8 mg/g MSG resulted in significant changes in serum total lipids, triglycerides, phospholipids, free fatty acids and blood glucose 31 d after cessation of exposure. Administration of 2 mg/...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90009-x
更新日期:1989-02-01 00:00:00
abstract::Clinical study showed that smoking during pregnancy deceased the thymus size in newborns. However, the long-term effect remains unclear. This study was aimed to observe the effects of prenatal nicotine exposure (PNE) on the development of thymus and the T-lymphocyte subpopulation in mice offspring from the neonatal to...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.12.015
更新日期:2019-04-01 00:00:00
abstract::The in vitro N-methylating capability of rabbit tissue cytosolic preparations, utilizing S-adenosyl-L-[methyl-3H]methionine as methyl donor, is described. Dialysed preparations from the lung, liver and kidney are capable of N-methylating 3- and 4-phenylpyridines and 3,3'- and 4,4'-bispyridyls; the corresponding 2-subs...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90213-4
更新日期:1986-12-01 00:00:00
abstract::The 2,4-dinitrophenylhydrazine (2,4-DNPH) derivatization method mainly used for the determination of airborne formaldehyde was extended for acetaldehyde, acetone, 2-butanone, and cyclohexanone, the next four carbonyl compounds of industrial importance. Sampling devices and sampling conditions were adjusted for the res...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00085-x
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induce...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.05.023
更新日期:2017-08-05 00:00:00
abstract::Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5 to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily. There was no treatment-related toxicity. Thus, effects on body weight gain, food...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90147-3
更新日期:1994-01-01 00:00:00
abstract::The US Environmental Protection Agency (EPA) in 1999 issued draft guidelines on carcinogen risk assessment, which included the use mode of action information in the risk assessment process. We have used the five stages of induction of toxicity as described by Aldridge to illustrate in the case of two drugs, tamoxifen ...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(03)00028-6
更新日期:2003-04-11 00:00:00
abstract::Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990s. In this study, we examined the effect of organoph...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.02.016
更新日期:2011-05-30 00:00:00
abstract::Administration of [14C]chlorferron in a single oral dose of 0.5 and 20 mg/kg body weight to female rats resulted in a urinary excretion of greater than 74% of the given dose during the first 24 h. Approx. 8% of the dose was eliminated in faeces within 7 days. 7 days after dosing, very low levels of [14C]chlorferron-de...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(81)90091-6
更新日期:1981-03-01 00:00:00
abstract:INTRODUCTION:An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of c...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.10.004
更新日期:2018-01-05 00:00:00
abstract::The skin absorption of aniline, aniline with 3% water content, and 1 and 2% aqueous aniline solutions was investigated in man. The time of exposure was 30 or 60 min. The absorbed amount of aniline was calculated on the basis of rho-aminophenol excretion in 24-h urine. The rate of aniline absorption from aqueous soluti...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90231-4
更新日期:1982-03-01 00:00:00
abstract::The involvement of neurotrophins after radiation injury during brain development were studied in pregnant mice (C 57/B1) exposed on gestation day 15 to X-ray doses of 0.02-2 Gy. Nerve growth factor protein (NGF) and different cholinergic markers were investigated on postnatal day 1 (P1) and day 21 (P21); in situ hybri...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(96)03827-1
更新日期:1997-01-15 00:00:00
abstract::The direct or indirect interference with GABA-mediated neurotransmission results in convulsive seizure activity in humans and experimental animals. When this convulsant effect is experimentally analyzed, it turns out to be a product of discrete and restricted cerebral sites of drug action. Depending upon the brain cir...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(92)90215-6
更新日期:1992-12-01 00:00:00
abstract::A low-Mr copper (Cu) and zinc (Zn)-binding protein was present in the liver of a control water lizard Triturus pyrrhogaster. Cadmium (Cd) accumulated in the liver of the animals after intramuscular injections of Cd salt and was bound to Cu- and Zn-binding protein of a single isoform that had properties characteristic ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90203-0
更新日期:1984-05-01 00:00:00
abstract::Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.10.013
更新日期:2012-01-05 00:00:00
abstract::Organophosphates are chemical pollutants that are existed widely in the environment, but the reactions of these agents with blood proteins are still not fully clarified. The current story was to analyze the static and dynamic interactions between human serum albumin (HSA) and phenthoate and then uncover the impact of ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.07.025
更新日期:2019-10-10 00:00:00
abstract::The effects of zinc on the lipid components of carp erythrocytes (Cyprinus carpio L.) were studied on red blood cells exposed to ZnSO4 (0.01-1 mM) for 20 h. The temperatures of the incubation medium were 5 and 20 degrees C for carp collected in winter and summer, respectively. It was observed that increase in the conc...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(02)00066-8
更新日期:2002-06-07 00:00:00
abstract::A rat bioassay has been developed to provide an objective approach for the identification and classification of upper and lower respiratory tract irritants, with particular emphasis on the concentration-dependent induction and regression of lesions characteristic of asthma, such as persisting non-specific airway hyper...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(96)03688-0
更新日期:1996-08-01 00:00:00
abstract::Acetylcholinesterase (AChE)-induced chewing movements, tremors, convulsions and hind limb abduction at doses of 50-85% LD50 in rats were monitored in order to determine whether the severity of these different signs would correlate with brain AChE levels and the time course of such a relationship. 30 min after subcutan...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90094-9
更新日期:1986-02-01 00:00:00
abstract::Chemical-peptide conjugation is the molecular initiating event in skin sensitization. The OECD test guideline uses a high-performance liquid chromatography/ultraviolet (HPLC/UV) detection method to quantify chemical-peptide conjugation in a direct peptide reactivity assay (DPRA), which measures the depletion of two sy...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.12.002
更新日期:2021-03-01 00:00:00
abstract::Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the pot...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.06.010
更新日期:2019-10-10 00:00:00
abstract::(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(98)00192-1
更新日期:1998-11-23 00:00:00
abstract::The chronic toxic effects of chromium (2.6 mg/1) on the carbohydrate metabolism of a teleost fish, Channa punctatus were examined after 60 and 120 days of exposure. After 60 days the lactic acid content of blood and muscles was increased but liver lactic acid content decreased. Liver glycogen was also depleted. The ac...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90003-6
更新日期:1983-04-01 00:00:00
abstract::Heart rate (HR) and body core temperature (Tco) were monitored in unanesthetized, unrestrained adult Sprague-Dawley rats following intraperitoneal administration of 0, 10, 30, or 60 mg/kg of the pesticide chlordimeform (CDM). Significant non-dose-related decreases were observed in both HR and Tco in all treated groups...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90208-6
更新日期:1987-02-01 00:00:00
abstract::Serum corticosterone levels were determined at intervals after i.p. injection of 1.8 mg cadmium (Cd)/kg body weight. Thymus weight decreased significantly 3 days after injection. The effect of Cd injection on serum corticosterone levels was almost indistinguishable from that of saline injection. Further, Cd-induced th...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90244-2
更新日期:1982-08-01 00:00:00