Effects of subchronic inhalation of low concentrations of nitrogen dioxide. I. The proximal alveolar region of juvenile and adult rats.

Abstract:

:Inhalation of nitrogen dioxide (NO2) produces injury to the epithelium of terminal airways and the alveoli proximal to the airways. Techniques were devised to isolate alveolar tissue from this region for morphometric studies to define the extent of alveolar septal injury caused by NO2. One-day-old and six-week-old rats were exposed to either room air or 0.5 ppm NO2 for 23 hr per day 7 days per week for 6 weeks. An additional group of 6-week-old rats were exposed to 2.0 ppm NO2 for the same duration. Two daily hour spikes to three times the background concentrations (0.5 to 1.5 ppm and 2.0 to 6.0 ppm) were applied Monday through Friday. At the end of the exposure, rat lungs were fixed by intratracheally infusing buffered 2% glutaraldehyde. Pieces of lung tissue were embedded in large plastic blocks which were softened with heat and thin (0.3 mm) sliced. Terminal bronchioles and their corresponding proximal alveolar regions were identified from the thin plastic slices, removed, and glued to cylindrical EM blocks for thin sectioning. Morphometric analysis revealed that epithelial injury occurred in all exposed animals. The juvenile rats which had been exposed to 0.5 ppm NO2 since 1 day of age exhibited changes in the characteristics of type II epithelial cells. These cells spread to cover more alveolar surface and became thinner. Adult animals exposed to 0.5 and 2.0 ppm NO2 showed changes in alveolar macrophages and in the alveolar interstitium in addition to changes in the epithelium. Animals exposed to 0.5 ppm NO2 showed spreading and hypertrophy of type II epithelial cells. Those animals exposed to the higher concentration of NO2 had similar changes in type II epithelial cells and in addition showed an increase in type I cell number. The type I epithelial cells were smaller and covered less alveolar surface area than normal type I cells, suggesting a regenerating population of type I cells. These results suggest that prolonged exposure to low concentrations of NO2 can cause injury to the alveolar epithelium indicated initially by spreading and hypertrophy of type II cells followed by differentiation into type I cells to compensate and repair the injury. Adult rats were as sensitive or more sensitive to NO2 injury than were juvenile rats.

journal_name

Toxicol Appl Pharmacol

authors

Chang LY,Graham JA,Miller FJ,Ospital JJ,Crapo JD

doi

10.1016/0041-008x(86)90321-2

subject

Has Abstract

pub_date

1986-03-30 00:00:00

pages

45-61

issue

1

eissn

0041-008X

issn

1096-0333

journal_volume

83

pub_type

杂志文章
  • Activation of 3,4,3',4'-tetrachlorobiphenyl to protein-bound metabolites by rat liver microsomal cytochrome P-448-containing monooxygenase system.

    abstract::The specificity of two major types of cytochrome P-450 of rat liver microsomes induced by phenobarbital (PB) and 3-methylcholanthrene (MC) toward activation of three 14C-labeled tetrachlorobiphenyl (TCB) isomers to protein-bound metabolites was examined by intact microsomal and reconstituted monooxygenase systems. The...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(83)90166-7

    authors: Shimada T,Sawabe Y

    更新日期:1983-09-30 00:00:00

  • Developmentally-regulated sodium channel subunits are differentially sensitive to alpha-cyano containing pyrethroids.

    abstract::Juvenile rats have been reported to be more sensitive to the acute neurotoxic effects of the pyrethroid deltamethrin than adults. While toxicokinetic differences between juveniles and adults are documented, toxicodynamic differences have not been examined. Voltage-gated sodium channels, the primary targets of pyrethro...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2008.04.017

    authors: Meacham CA,Brodfuehrer PD,Watkins JA,Shafer TJ

    更新日期:2008-09-15 00:00:00

  • Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205.

    abstract::The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell li...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2004.11.001

    authors: Gupta DD,Saha S,Chakrabarti MK

    更新日期:2005-08-01 00:00:00

  • Depletion of glutathione by benzo(a)pyrene metabolites, ionomycin, thapsigargin, and phorbol myristate in human peripheral blood mononuclear cells.

    abstract::Previous studies in this laboratory have shown that polycyclic aromatic hydrocarbons (PAHs) alter Ca2+ homeostasis and inhibit activation of both B and T lymphocytes obtained from rodents and humans. In the present studies, we demonstrate that alpha-naphthoflavone (ANF), an inhibitor of cytochrome P4501A activity, red...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1997.8113

    authors: Romero DL,Mounho BJ,Lauer FT,Born JL,Burchiel SW

    更新日期:1997-05-01 00:00:00

  • Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells.

    abstract::Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit a well defined cytotoxicological response from mammalian cell lines, the response increasing systematically with dendrimer generation and number of surface amino groups. In this work, using generation G4, G5, and G6 dendrimers, this syst...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2010.08.016

    authors: Mukherjee SP,Lyng FM,Garcia A,Davoren M,Byrne HJ

    更新日期:2010-11-01 00:00:00

  • Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone.

    abstract::Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2004.04.010

    authors: Johnson TE,Zhang X,Bleicher KB,Dysart G,Loughlin AF,Schaefer WH,Umbenhauer DR

    更新日期:2004-11-01 00:00:00

  • Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk.

    abstract::Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has eme...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2015.12.014

    authors: Costa PM,Fadeel B

    更新日期:2016-05-15 00:00:00

  • Advances in exposure and toxicity assessment of particulate matter: an overview of presentations at the 2009 Toxicology and Risk Assessment Conference.

    abstract::The 2009 Toxicology and Risk Assessment Conference (TRAC) session on "Advances in Exposure and Toxicity Assessment of Particulate Matter" was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academi...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.taap.2010.10.020

    authors: Gunasekar PG,Stanek LW

    更新日期:2011-07-15 00:00:00

  • Effect of cadmium on plasma aldosterone and serum corticosterone concentrations in male rats.

    abstract::Cadmium chloride (CdCl2) at a dose of 1 mg/kg of body weight was injected into male Wistar rats twice a day (12-hr intervals) for 7 consecutive days. A group of treated rats was maintained without any treatment for an additional period of 10 days and killed on the following day (on Day 18). Plasma aldosterone concentr...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(84)90346-6

    authors: Nishiyama S,Nakamura K

    更新日期:1984-12-01 00:00:00

  • Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus.

    abstract::A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used ...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2017.04.017

    authors: Yang CW,Chang HY,Hsu HY,Lee YZ,Chang HS,Chen IS,Lee SJ

    更新日期:2017-10-01 00:00:00

  • Carcinogenicity of formaldehyde and hydrogen chloride in rats.

    abstract::Previous studies in this laboratory have shown that the combined exposure of hydrogen chloride (HCI) and formaldehyde vapors (HCHO) elicited a significant incidence of nasal cancer in rats. In studies performed elsewhere, it has been demonstrated that exposure to formaldehyde alone induced a high nasal cancer response...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(85)90411-9

    authors: Sellakumar AR,Snyder CA,Solomon JJ,Albert RE

    更新日期:1985-12-01 00:00:00

  • Evidence for basolateral uptake of cadmium in the kidneys of rats.

    abstract::In three separate sets of studies, the effects of ureteral ligation and coadministration of cadmium with cysteine or glutathione (GSH) (in either a 4:1 or 2:1 ratio of thiol to cadmium) on the renal disposition of cadmium were assessed in rats 1 h after the administration of cadmium. In all experiments, co-administrat...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1999.8854

    authors: Zalups RK

    更新日期:2000-04-01 00:00:00

  • Protection of hepatocytes against death due to mitochondrial failure: effect of di-Calciphor on antimycin A-induced toxicity.

    abstract::Di-Calciphor is a synthetic derivative of prostaglandin B1 that protects against cerebral and cardiac ischemia apparently by preserving mitochondrial function. To determine whether di-Calciphor specifically protects against mitochondrial failure, we studied its effects on mitochondrial functions in hepatocytes treated...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1994.1087

    authors: Park Y,Devlin TM,Jones DP

    更新日期:1994-05-01 00:00:00

  • Response of rats to low levels of sarin.

    abstract::The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m(3) of sarin for 1 h/day for 1, 5, or 10 days under...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:

    authors: Henderson RF,Barr EB,Blackwell WB,Clark CR,Conn CA,Kalra R,March TH,Sopori ML,Tesfaigzi Y,Ménache MG,Mash DC

    更新日期:2002-10-15 00:00:00

  • Stress does not enable pyridostigmine to inhibit brain cholinesterase after parenteral administration.

    abstract::The peripherally acting cholinesterase inhibitor pyridostigmine was widely used during the Gulf War as a pretreatment against possible chemical warfare attack. Following consistent reports on long-term illness among Gulf War veterans, pyridostigmine was examined for its possible long-term effects. These effects were s...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.2000.8906

    authors: Grauer E,Alkalai D,Kapon J,Cohen G,Raveh L

    更新日期:2000-05-01 00:00:00

  • Acute trimethyltin intoxication in the monkey (Macaca fascicularis).

    abstract::Adult cynomolgus monkeys were administered trimethyltin (TMT) iv in dosages ranging from 0.75 to 4.0 mg TMT/kg and observed for behavioral changes. Animals were subsequently killed for light and electron microscopic examination. TMT showed a dose-related toxicity, with high dose animals (4.0 and 3.0 mg/kg) dying withi...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(85)90141-3

    authors: Reuhl KR,Gilbert SG,Mackenzie BA,Mallett JE,Rice DC

    更新日期:1985-07-01 00:00:00

  • Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes.

    abstract::Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected t...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2011.02.008

    authors: Strigun A,Wahrheit J,Beckers S,Heinzle E,Noor F

    更新日期:2011-04-15 00:00:00

  • Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.

    abstract::The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2,...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2007.07.013

    authors: Gracia T,Hilscherova K,Jones PD,Newsted JL,Higley EB,Zhang X,Hecker M,Murphy MB,Yu RM,Lam PK,Wu RS,Giesy JP

    更新日期:2007-12-01 00:00:00

  • Effects of dietary selenium species on Se concentrations in hair, blood, and urine.

    abstract::The effects of the chemical species and concentration of selenium (Se) in diets on the concentrations of Se in hair, blood serum, red blood cells (RBCs), and urine were studied to gain an insight into the toxicological and nutritional significance of different chemical forms of Se. Male Wistar rats were fed an Se-defi...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1998.8537

    authors: Shiobara Y,Yoshida T,Suzuki KT

    更新日期:1998-10-01 00:00:00

  • Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury.

    abstract::Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully un...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2011.06.001

    authors: Milatovic D,Gupta RC,Yu Y,Zaja-Milatovic S,Aschner M

    更新日期:2011-11-01 00:00:00

  • Mefenamic acid bi-directionally modulates the transient outward K+ current in rat cerebellar granule cells.

    abstract::The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K(+) current (I(A)) in cultured rat cerebellar granule ce...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2007.09.008

    authors: Zhang M,Shi WJ,Fei XW,Liu YR,Zeng XM,Mei YA

    更新日期:2008-02-01 00:00:00

  • Proposed mechanistic description of dose-dependent BDE-47 urinary elimination in mice using a physiologically based pharmacokinetic model.

    abstract::Polybrominated diphenyl ethers (PBDEs) have been used in a wide variety of consumer applications as additive flame retardants. In North America, scientists have noted continuing increases in the levels of PBDE congeners measured in human serum. Some recent studies have found that PBDEs are associated with adverse heal...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2013.09.007

    authors: Emond C,Sanders JM,Wikoff D,Birnbaum LS

    更新日期:2013-12-01 00:00:00

  • Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor α.

    abstract::Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation seque...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2020.115030

    authors: Böckers M,Paul NW,Efferth T

    更新日期:2020-07-15 00:00:00

  • Studies on the mechanism of uroporphyrinogen decarboxylase inhibition in hexachlorobenzene-induced porphyria in the female rat.

    abstract::Hexachlorobenzene (HCB)-induced porphyria occurs in female, but not male, rats after a delay of 35 days following HCB treatment. Uroporphyrinogen decarboxylase (UROD) inhibition has been proposed as a primary causative event. To determine whether there also exists a delay phase and a sexual dimorphism for UROD inhibit...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1006/taap.1997.8157

    authors: Mylchreest E,Charbonneau M

    更新日期:1997-07-01 00:00:00

  • 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice.

    abstract::4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed th...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2011.09.009

    authors: Park KL,Ko NY,Lee JH,Kim DK,Kim HS,Kim AR,Her E,Kim B,Kim HS,Moon EY,Kim YM,Kim HR,Choi WS

    更新日期:2011-12-01 00:00:00

  • Differential toxicity of heterocyclic aromatic amines and their mixture in metabolically competent HepaRG cells.

    abstract::Human exposure to heterocyclic aromatic amines (HAA) usually occurs through mixtures rather than individual compounds. However, the toxic effects and related mechanisms of co-exposure to HAA in humans remain unknown. We compared the effects of two of the most common HAA, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2010.03.008

    authors: Dumont J,Jossé R,Lambert C,Anthérieu S,Le Hegarat L,Aninat C,Robin MA,Guguen-Guillouzo C,Guillouzo A

    更新日期:2010-06-01 00:00:00

  • Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout.

    abstract::This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2nM [(3)H]2, 3, 7, 8-tetr...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2011.04.015

    authors: Curtis LR,Garzon CB,Arkoosh M,Collier T,Myers MS,Buzitis J,Hahn ME

    更新日期:2011-07-01 00:00:00

  • Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk.

    abstract::Alteration in the expression pattern of Nrf-2 and NFκB has been reported in ulcerative colitis (UC) in which functional crosstalk between these two critical pathways has been suggested. The ameliorative potential of the AT1R blocker olmesartan (OLM) on oxidative stress and inflammatory cytokines has received considera...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2018.12.020

    authors: Saber S,Khalil RM,Abdo WS,Nassif D,El-Ahwany E

    更新日期:2019-02-01 00:00:00

  • In vitro effects of benzene metabolites on mouse bone marrow stromal cells.

    abstract::Benzene exposure can result in bone marrow myelotoxicity. We examined the effects of benzene metabolites on bone marrow stromal cells of the hemopoietic microenvironment. Male B6C3F1 mouse bone marrow adherent stromal cells were plated at 4 X 10(6) cells per 2 ml of DMEM medium in 35-mm tissue culture dishes. The grow...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/0041-008x(84)90027-9

    authors: Gaido K,Wierda D

    更新日期:1984-10-01 00:00:00

  • HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells.

    abstract::Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondria...

    journal_title:Toxicology and applied pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.taap.2014.11.001

    authors: Fa S,Pogrmic-Majkic K,Samardzija D,Hrubik J,Glisic B,Kovacevic R,Andric N

    更新日期:2015-01-01 00:00:00