Abstract：
:Tetrandrine, a bisbenzylisoquinoline alkaloid, has demonstrated promising pharmacologic activities. The alkaloid has a great potential for clinical use, so a careful, thorough toxicity evaluation of the alkaloid is required. In the present study, 24 h acute toxicity of tetrandrine was evaluated in CD-1 mice. Single intraperitoneal doses of tetrandrine at 150 mg (0.24 mmol)/kg were found to cause alveolar hemorrhage and over 3-fold elevation of lactate dehydrogenase activity in bronchoalveolar lavage fluids. Ethidium-based staining showed loss of membrane integrity in significant numbers of cells in the lungs of the animals treated with the same doses of tetrandrine. As much as 60% reduction in cell viability was observed after 24 h of exposure to tetrandrine at 40 μM in human lung cell lines NL-20 and WI-38. Ketoconazole, an inhibitor of P450 3A, showed a protective effect on the pulmonary injury in mice given tetrandrine. A glutathione (GSH) conjugate derived from O-demethylated tetrandrine was detected in incubations of tetrandrine with NADPH- and GSH-supplemented human liver and mouse lung microsomes. The electrophilic metabolite trapped by GSH is considered to be a quinone methide derivative. The formation of the metabolite reactive to GSH was found to require the presence of NADPH. The coincubation of ketoconazole suppressed the generation of the GSH conjugate. Tetrandrine was incubated with a selection of recombinant human cytochrome P450 enzymes, and only P450s 3A4 and 3A5 were responsible for the production of the reactive metabolite. The results implicate a possible correlation between the formation of the quinone methide metabolite of tetrandrine and the pulmonary toxicity induced by tetrandrine.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Jin H,Li L,Zhong D,Liu J,Chen X,Zheng Jdoi
10.1021/tx200290ssubject
Has Abstractpub_date
2011-12-19 00:00:00pages
2142-52issue
12eissn
0893-228Xissn
1520-5010journal_volume
24pub_type
杂志文章abstract：:At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o-quinone metabolites of gallic acid or EGCG are causat...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00450
更新日期：2020-11-16 00:00:00
abstract：:Deoxynivalenol (DON) is a trichothecene mycotoxin that is produced by several species of Fusarium, which may infect grain crops. DON, as well as other type-B trichothecenes, contain an α,β-unsaturated carbonyl group that may react with sulfhydryl groups in, for example, amino acids and peptides. Such conjugates have b...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00385
更新日期：2020-02-17 00:00:00
abstract：:Solutions of synthetic fecapentaene 12 (FP-12) intended for carcinogenicity studies were found to decompose extremely rapidly during customary dosage procedures. Apparent half-lives as short as 15 min were observed. While rates and even the qualitative course of decomposition were surprisingly variable in replicate ex...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00009a007
更新日期：1989-05-01 00:00:00
abstract：:Free-radical oxidation of human plasma low-density lipoprotein (LDL) produces (carboxyalkyl)pyrrole (CAP) epitopes that were detected with enzyme-linked immunosorbent assays using antibodies raised against keyhole limpet hemocyanin (KLH)-bound 2-(omega-carboxyheptyl)-pyrrole (CHP) and 2-(omega-carboxypropyl)pyrrole (C...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx970112c
更新日期：1997-12-01 00:00:00
abstract：:Cytochrome P450 2F1 (P450 2F1) is expressed exclusively in the human respiratory tract and is implicated in 3-methylindole (3MI)-induced pneumotoxicity via dehydrogenation of 3MI to a reactive electrophilic intermediate, 3-methyleneindolenine (3-MEI). Studies of P450 2F1 to date have been limited by the failure to exp...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300281g
更新日期：2012-09-17 00:00:00
abstract：:There are discrepancies about whether chlorpyrifos is able to induce neurodevelopmental toxicity or not. We previously reported alterations in the pattern of expression of biomarker genes of differentiation in D3 mouse embryonic stem cells caused by chlorpyrifos and its metabolites chlorpyrifos-oxon and 3,5,6-trichlor...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500051k
更新日期：2014-09-15 00:00:00
abstract：:The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unide...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00035a007
更新日期：1993-09-01 00:00:00
abstract：:Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hy...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00286
更新日期：2019-04-15 00:00:00
abstract：:Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products. Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress. However, the underlying mecha...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400036v
更新日期：2013-03-18 00:00:00
abstract：:Exposure assessment in in vitro cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00067
更新日期：2020-07-20 00:00:00
abstract：:Tocopherols (alpha-, beta-, gamma-, and delta-Toc) and tocopheryl quinones (alpha-, beta-, gamma-, and delta-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, a potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex, possess a common ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx900333f
更新日期：2010-01-01 00:00:00
abstract：:Retinyl palmitate (RP) is frequently used as an ingredient in cosmetics and other retail products. We previously reported that, under UVA light irradiation, RP is facilely decomposed into multiple products, including anhydroretinol (AR) and 5,6-epoxyretinyl palmitate (5,6-epoxy-RP). We also determined that combined tr...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0600907
更新日期：2006-11-01 00:00:00
abstract：:N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) is an orally administrated drug widely used in the chemotherapy of chronic lymphocytic leukemia. We have recently described a new metabolic path for the decomposition of 1 in human gastric juice based on its reactions with saliva-derived thiocyanate io...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980122t
更新日期：1998-11-01 00:00:00
abstract：:During our ongoing studies of the reactions of toluene diisocyanate (2,4- and 2,6-diisocyanatotoluene, TDI) in vivo, it became apparent that reactive form(s) of these diisocyanates reach(es) the circulatory system after passage through the respiratory system. Based on recent work by others regarding the transcarbamoyl...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960201+
更新日期：1997-04-01 00:00:00
abstract：:The metabolic fates of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two-electron oxidation product, the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), have been examined in mouse brain and liver tissue fractions. Incubations of MPTP (50 microM and 1 mM) with mouse brain...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00003a010
更新日期：1988-05-01 00:00:00
abstract：:The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. The lesion disrupts replication and gives rise to mutations that are dependent upon the identity of the upstream nucleotide. Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9003984
更新日期：2010-04-19 00:00:00
abstract：:Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA-protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500068v
更新日期：2014-06-16 00:00:00
abstract：:The neurotrophic factor pleiotrophin (PTN) is upregulated in different brain areas after the administration of different drugs of abuse, including psychostimulants. PTN has been shown to prevent cocaine-induced cytotoxicity in NG108-15 and PC12 cells. We previously demonstrated that specific phosphoproteins related to...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00130
更新日期：2015-07-20 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：:The present study investigated the oxidative metabolism of 2-naphthyl isothiocyanate catalyzed by rat liver microsomes. Incubation of 2-naphthyl isothiocyanate, microsomes, and NADPH yielded either N,N'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ure...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00030a010
更新日期：1992-11-01 00:00:00
abstract：:The mechanism of formation of etheno (epsilon) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1H NMR assignments of the epsilon protons of 1,N2-epsilon-Guo (G...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00038a014
更新日期：1994-03-01 00:00:00
abstract：:Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the carcinogenicity of...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx025558u
更新日期：2002-09-01 00:00:00
abstract：:Enzymatic methylation of cytosine residues in DNA, in conjunction with covalent histone modifications, establishes an epigenetic code essential for the proper control of gene expression in higher organisms. Once established during cellular differentiation, the epigenetic code must be faithfully transmitted to progeny ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx900027w
更新日期：2009-06-01 00:00:00
abstract：:Estrogens, including the natural hormones estrone (E(1)) and estradiol (E(2)), are thought to be involved in tumor induction. Specifically, catechol estrogen quinones (CEQs) derived from the catechol estrogens 4-hydroxyestrone (4-OHE(1)) and 4-hydroxyestradiol (4-OHE(2)) react with DNA and form DNA adducts (Cavalieri,...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx020088p
更新日期：2003-03-01 00:00:00
abstract：:Evidence from laboratory studies and clinical trials suggests that plant-derived polyphenolic compounds such as curcumin, resveratrol, or phloretin might be useful in the treatment of certain diseases (e.g., Alzheimer's disease) and acute tissue injury states (e.g., spinal cord trauma). However, despite this potential...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.6b00300
更新日期：2016-12-19 00:00:00
abstract：:Metabolic bioactivation, glutathione depletion, and covalent binding are the early hallmark events after acetaminophen (APAP) overdose. However, the subsequent metabolic consequences contributing to APAP-induced hepatic necrosis and apoptosis have not been fully elucidated. In this study, serum metabolomes of control ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800464q
更新日期：2009-04-01 00:00:00
abstract：:E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative bur...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00171
更新日期：2019-06-17 00:00:00
abstract：:Polychlorinated biphenyls (PCBs) are one of the most refractory environmental pollutants. Because of their ubiquitous existence in the biological systems (including human body), it is important to investigate their toxic behavior. Our previous findings demonstrated that a high reactive metabolite of PCB, namely PCB29-...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.8b00376
更新日期：2019-06-17 00:00:00
abstract：:The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. The goal was to gain more detailed mechanistic insights into the t...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx800253x
更新日期：2009-01-01 00:00:00
abstract：:Vinyl chloride and acrolein are important industrial chemicals. Both form DNA adducts, vinyl chloride after enzymatic oxidation to chlorooxirane and acrolein by direct reaction. Reaction at the N(2) position of guanine is a major pathway. The resulting 2-oxoethyl and 3-oxopropyl adducts cyclize spontaneously to hydrox...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990167+
更新日期：2000-05-01 00:00:00
