Abstract:
:Titanium dioxide nanoparticles (Nano-TiO2) are gradually being used extensively in clinical settings, industry, and daily life. Accumulation studies showed that Nano-TiO2 exposure is able to cause injuries in various animal organs, including the lung, liver, spleen, and kidney. However, it remains unclear whether exposure of Nano-TiO2 by inhalation causes renal fibrosis. Here, we investigated the role of reactive oxygen species (ROS)/reactive nitrogen species (RNS) related signaling molecules in chronic renal damage after Nano-TiO2 inhalation in mice. Mice were treated with Nano-TiO2 (0.1, 0.25, and 0.5 mg/week) or microparticle-TiO2 (0.5 mg/week) by nonsurgical intratracheal instillation for 4 weeks. The results showed that Nano-TiO2 inhalation increased renal pathological changes in a dose-dependent manner. No renal pathological changes were observed in microparticle-TiO2-instilled mice. Nano-TiO2 (0.5 mg/week) possessed the ability to precipitate in the kidneys, determined by transmission electron microscopy and increased serum levels of blood urea nitrogen. The expressions of markers of ROS/RNS and renal fibrosis markers, including nitrotyrosine, inducible nitric oxide synthase, hypoxia inducible factor-1α (HIF-1α), heme oxygenase 1, transforming growth factor-β (TGFβ), and collagen I, determined by immunohistochemical staining were increased in the kidneys. Furthermore, Nano-TiO2-induced renal injury could be mitigated by iNOS inhibitor aminoguanidine and ROS scavenger N-acetylcysteine treatment in transcription level. The in vitro experiments showed that Nano-TiO2 significantly and dose-dependently increased the ROS production and the expressions of HIF-1α and TGFβ in human renal proximal tubular cells, which could be reversed by N-acetylcysteine treatment. Taken together, these results suggest Nano-TiO2 inhalation might induce renal fibrosis through a ROS/RNS-related HIF-1α-upregulated TGF-β signaling pathway.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Huang KT,Wu CT,Huang KH,Lin WC,Chen CM,Guan SS,Chiang CK,Liu SHdoi
10.1021/tx500287fsubject
Has Abstractpub_date
2015-03-16 00:00:00pages
354-64issue
3eissn
0893-228Xissn
1520-5010journal_volume
28pub_type
杂志文章abstract::The purpose of this study was to investigate the degree of chlorination of catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two human breast carcinoma cell lines. Results indicated that with the addition of the transition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0498511
更新日期:2005-02-01 00:00:00
abstract::Tetrabromobisphenol A, a brominated flame retardant, is increasingly prevalent worldwide and presents a potential health risk. Adjusted animal biomonitoring equivalents of tetrabromobisphenol A after orally administered doses in humanized-liver mice were scaled up to humans using known species allometric scaling facto...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00358
更新日期:2020-11-16 00:00:00
abstract::Implementation of the Clinical Data Interchange Standards Consortium (CDISC)'s Standard for Exchange of Nonclinical Data (SEND) by the United States Food and Drug Administration Center for Drug Evaluation and Research (US FDA CDER) has created large quantities of SEND data sets and a tremendous opportunity to apply la...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00317
更新日期:2020-12-16 00:00:00
abstract::A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx990098z
更新日期:1999-11-01 00:00:00
abstract::The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9002758
更新日期:2009-10-01 00:00:00
abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed during the cooking of meats. PhIP is a potential human carcinogen: it undergoes metabolic activation to form electrophilic metabolites that bind to DNA and proteins, including serum albumin (SA). The structures of Ph...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300253j
更新日期:2012-10-15 00:00:00
abstract::The issue of the safety of drug metabolites in humans is a complex one. In this commentary, a proposal is made regarding how to deal with drug metabolites observed in humans such that the safety of these molecules can be assured. The human radiolabeled ADME study, in which metabolites are identified and quantified in ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0602012
更新日期:2006-12-01 00:00:00
abstract::Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping fa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00423
更新日期:2017-02-20 00:00:00
abstract::A diverse series of polarized alpha,beta-unsaturated and related compounds were evaluated for reactivity with a spectrophotometric assay using the sulfhydryl group in the form of the cysteine residue of the tripeptide GSH as a model nucleophile. The reactive end point (RC 50) calculations were compared to previously d...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700212u
更新日期:2007-09-01 00:00:00
abstract::beta-Carotene and other carotenoids are thought to exert disease preventive actions by scavenging reactive free radicals, but the mechanisms of these reactions are poorly understood. We detected products formed by reaction of beta-carotene with alkoxyl, and alkylperoxyl free radicals generated by thermolysis of azobis...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950151t
更新日期:1996-01-01 00:00:00
abstract::Previous studies have demonstrated that reactive dicarbonyl compounds [e.g., methylglyoxal (MGO) and glyoxal (GO)] irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its subsequent compli...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700190s
更新日期:2007-12-01 00:00:00
abstract::Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx4002868
更新日期:2013-12-16 00:00:00
abstract::4-Carboxyl-substituted analogues of trans-3'-hydroxycotinine were synthesized to be covalently linked to macromolecules for antibody production. 3-Pyridyl-N-methylnitrone was condensed with dimethyl fumarate to give two isomeric isoxazolidines. Hydrogenolysis of the major product [2RS-(2 alpha,3 alpha,3 beta)]-3-carbo...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00023a006
更新日期:1991-09-01 00:00:00
abstract::We investigated the effect of a series of Maillard reaction products formed from carbohydrates under household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2H)-furanone (1) was found to potently enhance the proliferation of human tumor cells. In contrast, the Maillard-type chro...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025531a
更新日期:2003-01-01 00:00:00
abstract::Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5'-cyclo-2'-deoxyguan...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2005053
更新日期:2012-02-20 00:00:00
abstract::The pharmacodynamics of rat hepatic cytochrome P450 2B (P450 2B) induction by phenobarbital (PB) and two structural congeners, dl-5-ethyl-5-phenylhydantoin (EPH) and dl-5-ethyl-5-phenyloxazolidinedione (EPO), were investigated. The in vivo induction of P450 2B was probed in F344/NCr rats by measuring immunoreactive he...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00032a008
更新日期:1993-03-01 00:00:00
abstract::Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators of their toxic side-effects. Two alternative metabolic pathways known to be involved in the generation of reactive acylating metabolites of carboxylic acids are acyl glucuronidation and acyl-C...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx020013l
更新日期:2002-10-01 00:00:00
abstract::Chemical and physical characterization of transported evolving aerosols in an in vitro system is complex. The challenges include appropriate sampling sensitivity, measurement capabilities, and performing online measurements of constituents in the flowing aerosol during exposure. We assessed the performance of single-p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00381
更新日期:2020-02-17 00:00:00
abstract::Cyclic imides are known for their antitumor activity, especially the naphthalimide derivatives, such as Mitonafide and Amonafide. Recently, we have demonstrated the cytotoxic effect of a series of naphthalimide derivatives against B16F10 melanoma cells. On the basis of this fact, we have developed a study starting fro...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400284r
更新日期:2013-12-16 00:00:00
abstract::The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromiu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00018a016
更新日期:1990-11-01 00:00:00
abstract::For decades, many studies have linked maternal smoking to an increased risk of preterm birth. As a result, the scientific community has long hypothesized that exposure to environmental tobacco smoke (ETS), commonly referred to as second-hand smoke, is also associated with an increased risk of preterm birth. Multiple s...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00054
更新日期:2017-07-17 00:00:00
abstract::Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidel...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.7b00224
更新日期:2017-11-20 00:00:00
abstract::Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac have been proposed to be caused by the generation of reactive acyl glucuronides and oxidative metabolites. For the oxidative metabolism of diclofenac by cytochromes P450 at least five different reactive intermediates have been proposed p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400204d
更新日期:2013-11-18 00:00:00
abstract::The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ*+, O(2)*-, H(2)O(2), and secondary.OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predomin...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0155956
更新日期:2002-05-01 00:00:00
abstract::The primary products of one-electron oxidation of clozapine and olanzapine, very effective atypical antipsychotic drugs, have been spectroscopically characterized. The oxidation process has been studied under glassy matrix conditions and by a pulse radiolysis technique in aqueous solution. The rate constants for the o...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700128c
更新日期:2007-08-01 00:00:00
abstract::The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00409
更新日期:2017-01-17 00:00:00
abstract::1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300017s
更新日期:2012-07-16 00:00:00
abstract::The current study examined the bioactivation potential of a nonpeptidyl thrombopoietin receptor agonist, 1-(3-chloro-5-((4-(4-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)pyridine-2-yl)piperidine-4-carboxylic acid (1), containing a 2-carboxamido-4-arylthiazole moiety in the core structure. Toxicological ris...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700270r
更新日期:2007-12-01 00:00:00
abstract::Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx1002595
更新日期:2010-11-15 00:00:00
abstract::Alzheimer's disease, the most common cause of dementia, is at epidemic proportions (15 to 44% depending on age, of those age 65 to 84) in the U.S. and other developed countries but remains relatively rare in undeveloped countries. Surprisingly, solid historical data reveal the epidemic is a creature of the last centur...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.6b00373
更新日期:2017-03-20 00:00:00