Abstract:
:A multi-compartment physiologically based pharmacokinetic (PBPK) model was developed to describe the behavior of Cr(III) and Cr(VI) in rats and mice following long-term oral exposure. Model compartments were included for GI lumen, oral mucosa, forestomach/stomach, small intestinal mucosa (duodenum, jejunum, ileum), blood, liver, kidney, bone, and a combined compartment for remaining tissues. Data from ex vivo Cr(VI) reduction studies were used to characterize reduction of Cr(VI) in fed rodent stomach fluid as a second-order, pH-dependent process. For model development, tissue time-course data for total chromium were collected from rats and mice exposed to Cr(VI) in drinking water for 90 days at six concentrations ranging from 0.1 to 180 mg Cr(VI)/L. These data were used to supplement the tissue time-course data collected in other studies with oral administration of Cr(III) and Cr(VI), including that from recent NTP chronic bioassays. Clear species differences were identified for chromium delivery to the target tissue (small intestines), with higher concentrations achieved in mice than in rats, consistent with small intestinal tumor formation, which was observed upon chronic exposures in mice but not in rats. Erythrocyte:plasma chromium ratios suggest that Cr(VI) entered portal circulation at drinking water concentrations equal to and greater than 60 mg/L in rodents. Species differences are described for distribution of chromium to the liver and kidney, with liver:kidney ratios higher in mice than in rats. Overall, the PBPK model provides a good description of chromium toxicokinetics, with model predictions for tissue chromium within a factor of 3 for greater than 80% of measurements evaluated. The tissue data and PBPK model predictions indicate a concentration gradient in the small intestines (duodenum > jejunum > ileum), which will be useful for assessing the tumor response gradient observed in mouse small intestines in terms of target tissue dose. The rodent PBPK model presented here, when used in conjunction with a human PBPK model for Cr(VI), should provide a more robust characterization of species differences in toxicokinetic factors for assessing the potential risks associated with low-dose exposures of Cr(VI) in human populations.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Kirman CR,Hays SM,Aylward LL,Suh M,Harris MA,Thompson CM,Haws LC,Proctor DMdoi
10.1016/j.cbi.2012.08.016subject
Has Abstractpub_date
2012-10-25 00:00:00pages
45-64issue
1eissn
0009-2797issn
1872-7786pii
S0009-2797(12)00154-8journal_volume
200pub_type
杂志文章abstract::The toxicity of halogenated alkanes originates from their metabolism by cytochrome P-450 which leads to the formation of reactive intermediates. In particular, peroxyl radicals derived from the halogenated compounds are believed to induce peroxidative chain degradation of lipids. To examine this hypothesis, radical re...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(85)80170-8
更新日期:1985-08-01 00:00:00
abstract::The apoptotic/necrotic changes in isolated human peripheral blood mononuclear cells (MNCs) subjected to hydrogen peroxide (H2O2), cyanate (NaOCN) and their combination were examined. The mitochondrial potential (ΔΨm), the activities of caspases (-2, -3, -6, -8 and -9) and the level of carbonyls and amino groups in pro...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.04.007
更新日期:2017-05-25 00:00:00
abstract::Treatment of a lysosome-rich fraction from liver with 2-chloroethylethyl sulfide resulted in a dose-dependent release of arylsulfatase. The inclusion of Ca2+ enhanced the enzyme release by approximately 2.3-fold. The enhancing effect of Ca2+, showing an EC50 value of 30 mM, was mimicked by neither Mg2+ nor Mn2+. Studi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(95)03618-v
更新日期:1995-08-18 00:00:00
abstract::Data has been published showing that in heterotetrameric liver mitochondrial aldehyde dehydrogenase composed of the active (E487) and the inactive Oriental-variant (K487) subunit, the Oriental variant was dominant and caused the inactivation of the E487 subunit. The published structures of the enzyme showed that the g...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(00)00221-0
更新日期:2001-01-30 00:00:00
abstract::Mammalian organisms possess two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear explanation for this dual expression of acetylcholine-hydrolyzing enzymes is still missing. Better knowledge on how these two enzymes respond to various physiological or pha...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(99)00045-9
更新日期:1999-05-14 00:00:00
abstract::The distribution and metabolism of the environmental pollutant 1-nitropyrene was studied in C57B1/6N mice following oral or intraperitoneal dosing. When administered by gavage, 1-nitropyrene and its metabolites demonstrated biphasic elimination kinetics from the blood, with half-lives of 0.3 and 1.8 days and a distrib...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)03574-r
更新日期:1995-04-14 00:00:00
abstract::It is known that procymidone modifies sexual differentiation in vivo and in vitro, and that it induces vitellogenin (Vtg) synthesis in primary cultured rainbow trout hepatocytes. The aim of this study was to evaluate the mechanism underlying this latter in vitro estrogenic action. The cells were treated for 24 h with ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2003.12.006
更新日期:2004-03-15 00:00:00
abstract::Overactivation of N-methyl-D-aspartate (NMDA) receptors has been associated with neurodegenerative disorders such as Alzheimer's disease (AD), cerebral vascular disorders and amyotrophic lateral sclerosis (ALS). We have previously designed and synthesized a series of memantine nitrate and some of them have shown vesse...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109020
更新日期:2020-07-01 00:00:00
abstract::In cancer, a high flux of oxidants not only depletes the cellular thiols, but damages the whole cell as well. Epidemiological studies suggest green tea may mitigate cancers in human and animal models for which several mechanisms have been proposed. In the present investigation, the levels of cellular thiols such as re...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2004.06.006
更新日期:2004-10-15 00:00:00
abstract::A single intravenous injection of methylazoxymethanol (MAM) acetate in doses of either 20 or 35 mg/kg body weight to male Sprague-Dawley rats induced altered liver cell foci and later, liver neoplasms in a dose related manner. Sequential observations in the rats given 35 mg/kg and thereafter fed an iron-loading diet r...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(86)80083-7
更新日期:1986-04-01 00:00:00
abstract::Resistance to chemotherapeutic agent is a major cause of treatment failure in patients with cancer. In many cases, the primaly mechanism leading to a multidrug-resistant phenotype is the plasma-membrane localized overexpression of drug efflux transporters, such as P-glycoprotein. However, acidic intracellular organell...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(01)00157-0
更新日期:2001-07-31 00:00:00
abstract::The biological and physicochemical effects of reacting bacteriophages R17 and T7 with acetoxy-dimethylnitrosamine (ADMN) have been studied. The rate-determining step in the reactions appeared to be the loss of the acetoxy group by hydrolysis, the hydroxymethyl-methylnitrosamine generated decomposing rapidly to give a ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(76)90019-3
更新日期:1976-07-01 00:00:00
abstract::Evidence for the reversible binding of paraquat to calf thymus DNA has been obtained using equilibrium dialysis and thermal melting point determinations. The data indicated the presence of at least two populations of binding site with affinity constants of 6.2 X 10(4) and 7.1 X 10(3) M-1, respectively. The binding cap...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(87)90035-4
更新日期:1987-02-01 00:00:00
abstract::Exposure to perfluorocarboxylic acids, pthalate esters, and some hypolipidemic agents results in the proliferation of peroxisomes in the rodent liver. The structural diversity of these compounds suggests mechanistic diversity in their toxicity as well. To establish reliable biomarkers of peroxisome proliferation (PP) ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(95)03661-x
更新日期:1996-01-05 00:00:00
abstract::PC12 is a well studied cell model for neuronal differentiation. AChE is also considered as a marker for neuronal differentiation. In this study, we detected the change of AChE activity during the NGF induced differentiation of PC 12 cells, and targeted on the ratio of the activity of AChE on the cell surface, and foun...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.08.003
更新日期:2016-11-25 00:00:00
abstract::Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti-cancer and anti-inflammatory properties. In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and CYP3A, in rats. Lineweaver...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2013.02.005
更新日期:2013-04-25 00:00:00
abstract::Melatonin is a hormone produced in animals by the pineal gland and in plants under stress. Melatonin research has expanded rapidly, affecting an impressive enhancement in the understanding of its functions in plants and animals. However, far less focus has been directed to clarifying the nature of melatonin dose-respo...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/j.cbi.2018.12.008
更新日期:2019-02-01 00:00:00
abstract::In CF1 mice lindane treatment led to a significant increase in liver tumor incidence whilst in Osborne-Mendel rats it was not carcinogenic. Although somewhat less clear, the test in B6C3F1 mice led to the conclusion that under the conditions of the bioassay lindane was not carcinogenic for this strain. In this study, ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(82)90024-2
更新日期:1982-05-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) chemoresistance, which is regarded as a kind of stress management reaction to chemotherapy drugs, severely hinders the therapy outcomes of HCC treatment. Stress management is generally achieved by activating certain signal pathways and chemical factors, among which, nuclear factor-E2-rel...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/j.cbi.2017.12.014
更新日期:2018-01-25 00:00:00
abstract::Lanthanides (Ln) were known to induce cell apoptosis, which might be the results of their effects on mitochondria (MT). This study was trying to clarify the role of MT and reactive oxygen species (ROS) in Ln-induced apoptosis. We found that micromolar or lower concentration of La(3+), Gd(3+) and Yb(3+) bound to MT and...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(03)00072-3
更新日期:2003-07-25 00:00:00
abstract::The glutathione-S-transferases (GST) are a major contributor to the eukaryotic cell's defences against chemical and oxidative stress. However, the role of individual GST isoenzymes in conferring resistance to xenobiotics has not been fully determined. We have examined the effect of the rat GSTA5 isoenzyme in the detox...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(02)00023-6
更新日期:2002-05-20 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the responses to toxic environmental chemicals such as TCDD or dioxin-like PCBs. To regulate gene expression, the AhR requires its binding partner, the aryl hydrocarbon receptor nuclear translocator (ARNT). ARNT is als...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/j.cbi.2014.05.001
更新日期:2014-07-25 00:00:00
abstract::The molecular biology and enzymology of aldehyde dehydrogenase (ALDH) have been extensively investigated. However, most of the studies have been confined to the mammalian forms, while the sub-mammalian vertebrate ALDHs are relatively unexplored. In the present investigation, an ALDH was purified from the hepatopancrea...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(00)00231-3
更新日期:2001-01-30 00:00:00
abstract::The transformation of the hexachloro-1,3-butadiene metabolite S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (PCBC) by bacterial cysteine conjugate beta-lyase (beta-lyase) and by N-dodecylpyridoxal bromide (PLP-Br) was investigated using GC/MS to identify products formed. PCBC was transformed by both bacterial be...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(88)90093-2
更新日期:1988-01-01 00:00:00
abstract::Quinone methides are a class of reactive, electrophilic compounds which are capable of alkylating cellular macromolecules. They are formed during xenobiotic biotransformation reactions and are hypothesized to mediate the toxicity of a large number of quinone antitumor drugs as well as several alkylphenols. In addition...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/0009-2797(93)90117-h
更新日期:1993-02-01 00:00:00
abstract:BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is one of the most common lethal tumors with a high recurrence rate and low survival rate. Therefore, an urgent need exists for novel and effective treatment strategies for HNSCC patients. METHODS:Osthole, a natural ingredient extracted from Cnidium monnieri (L....
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2019.108934
更新日期:2020-01-25 00:00:00
abstract::The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this re...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(78)90090-x
更新日期:1978-12-01 00:00:00
abstract::Selenium compounds such as methylseleninic acid (MSA) and sodium selenite (SS) have been widely evaluated as potential anti-cancer agents in the clinical setting. Primary effusion lymphoma (PEL) is a non-Hodgkin's B-cell lymphoma, associated with immunosuppressed individuals, such as post-transplant or AIDS patients. ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.01.027
更新日期:2017-03-25 00:00:00
abstract::The current experimental work deals with the immunomodulatory studies on the extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene induced lung cancer in male Swiss albino mice. In our previous study, we reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal along with pa...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.11.003
更新日期:2006-02-25 00:00:00
abstract::Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to GO with large size (den...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109325
更新日期:2021-01-05 00:00:00