Abstract：
:This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these, BA was the most effective, increasing cytochrome P450 dependent metabolism 64-fold and DT-diaphorase activity 1.6-fold. R did not cause an increase in any of the enzyme activities measured and, in fact inhibited glutathione peroxidase activity. PB and DEX increased NADPH cytochrome c reductase activity but had no effect on either DT-diaphorase or cytochrome P450 dependent activities. BA potentiated the cytotoxicity of mitoxantrone in terms of leakage of lactate dehydrogenase (LDH) activity and loss of reduced glutathione (GSH) and protein from cultures. PB had a smaller potentiating effect on cytotoxicity and DEX had no effect. Studies with the enzyme inhibitors, dicoumarol (inhibits DT-diaphorase) and metyrapone (inhibits cytochrome P450), indicate that at least two reactive species are involved in mitoxantrone cytotoxicity. One intermediate, formed by cytochrome P450, caused LDH leakage and GSH depletion. Formation of the second intermediate was catalysed by DT-diaphorase and this hydroquinone caused loss of intracellular protein and GSH. We propose that autooxidation of the hydroquinone resulting in generation of reactive oxygen species contributes to mitoxantrone cytotoxicity. Concomitant exposure to inducing agents may alter the cytotoxicity associated with many cytotoxic drugs, not just mitoxantrone, and this is an important consideration as many cytotoxics have a narrow therapeutic index.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Li SJ,Rodgers EH,Grant MHdoi
10.1016/0009-2797(94)03603-6subject
Has Abstractpub_date
1995-07-14 00:00:00pages
101-18issue
2eissn
0009-2797issn
1872-7786pii
0009-2797(94)03603-6journal_volume
97pub_type
杂志文章abstract：:2-Nitropropane (2-NP) is a genotoxicant and hepatocarcinogen in rodents. Conversion to propane 2-nitronate (P2N), the anion of the tautomeric aci form of 2-NP, seems to be a pivotal part of the mechanism by which 2-NP causes its toxicity. We tested the hypothesis that the tautomeric equilibrium is influenced by enzyme...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(95)03671-7
更新日期：1996-01-05 00:00:00
abstract：:Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.05.009
更新日期：2014-08-05 00:00:00
abstract：:Prostate (CaP) cancer is the second-leading cause of cancer-related mortality in men in Western societies. Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2016.10.002
更新日期：2016-12-25 00:00:00
abstract：:Administration of hepatotoxic doses of allyl alcohol and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) TO adult male rats produced periportal necrosis and functional derangement of the hepatic endoplasmic reticulum within 24 h. The rates of N-demethylation of ethylmorphine and p-hydroxylation of aniline were decreased 6 ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90159-9
更新日期：1976-10-02 00:00:00
abstract：:Bis(12)-hupyridone (B12H), derived from the Chinese medicinal component huperzine A, was originally designed as a novel acetylcholinesterase (AChE) inhibitor. In this paper, we report that B12H (24-h pretreatment) effectively blocked glutamate-induced neuronal excitotoxicity in cerebellar granule neurons (CGNs). Howev...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.10.003
更新日期：2013-03-25 00:00:00
abstract：:Inflammation, oxidative stress and altered mucosal barrier permeability are potential etiopathological or triggering factors for inflammatory bowel disease (IBD). In this study, the therapeutic potential of Mangiferin was investigated in vivo in mouse model of colitis and also attempts were made to understand mechanis...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.04.033
更新日期：2016-06-25 00:00:00
abstract：:Dehydrogenase/reductase (SDR family) member 7 (DHRS7, retSDR4, SDR34C1) is a previously uncharacterized member of the short-chain dehydrogenase/reductase (SDR) superfamily. While human SDR members are known to play an important role in various (patho)biochemical pathways including intermediary metabolism and biotransf...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.11.003
更新日期：2014-01-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2010.04.007
更新日期：2010-11-05 00:00:00
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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：:20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.11.008
更新日期：2018-01-05 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
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/s0009-2797(02)00071-6
更新日期：2002-09-20 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.10.007
更新日期：2009-01-15 00:00:00
abstract：:The structure of the covalent adduct formed in vitro between [14C]-acetaminophen ([14C]APAP) and bovine serum albumin (BSA) has been investigated with the aid of new analytical methodology. The APAP-BSA adduct, isolated from mouse liver microsomal incubations to which the radiolabeled drug and BSA had been added, was ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(85)80093-4
更新日期：1985-02-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.01.017
更新日期：2017-10-01 00:00:00
abstract：:Pineal hormone melatonin is an important regulator of endocrine and circadian rhythms in vertebrates. Since liver is assumed to be the major organ in the metabolism of this indole hormone, we investigated the effect of the known Ah-receptor agonist, 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on melatonin metabolism i...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00153-8
更新日期：2000-06-01 00:00:00
abstract：:Osteoporosis is a major global public health problem. Aluminum (Al) exposure inhibits osteoblast mineralization and induces osteoporosis. However, the exact mechanism is not fully understood. The transforming growth factor β1 (TGF-β1)/Smad pathway is a major signaling cascade in regulating osteoblast mineralization. T...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.11.027
更新日期：2016-01-25 00:00:00
abstract：:In the present study, the inhibition of human glutathione S-transferase P1-1 (GSTP1-1) by the flavonoid quercetin has been investigated. The results show a time- and concentration-dependent inhibition of GSTP1-1 by quercetin. GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 microM quercetin or 2 h...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(02)00250-8
更新日期：2003-05-06 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00090-3
更新日期：1999-06-01 00:00:00
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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
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.09.021
更新日期：2015-12-05 00:00:00
abstract：:Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin-glycoprotein complex (DGC). Through laminin-2, the DGC bridges the muscle cytoskeleton and th...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.08.001
更新日期：2013-03-25 00:00:00
abstract：:Exposure to metals and metalloids including arsenic, cadmium, mercury, and nickel has been a worldwide health problem for several decades. The aim of this study was to learn how metal-induced oxidative stress triggers cell proliferation, a process of great significance for cancer. NADPH oxidase (NOX) activity and cell...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.10.034
更新日期：2014-12-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.12.038
更新日期：2015-06-05 00:00:00
abstract：:Numerous studies have revealed that gamma-linolenic acid (GLA) possesses effective tumoricidal properties while not inducing damage to normal cells or creating harmful systemic side effects. It can exert anti-tumor efficacy against a variety of cancers including leukemia. However, little is known about the effects of ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.05.019
更新日期：2006-08-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.04.007
更新日期：2012-06-25 00:00:00
abstract：:Treatment of isolated mitochondria from rat hepatoma tumor cells (AS-30D) with the oxidant, t-butyl hydroperoxide (tBuOOH, 1 or 5 mumol/ml) resulted in the oxidation of glutathione (GSH to GSSG) and the formation of protein-glutathione mixed disulfides (ProSSG). The GSSG was retained inside of the hepatoma mitochondri...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90073-t
更新日期：1992-09-28 00:00:00
abstract：:The Nuclear Factor-kappa B (NF-κB) pathway is vital for immune system regulation and pro-inflammatory signaling. Many inflammatory disorders and diseases, including cancer, are linked to dysregulation of NF-κB signaling. When macrophages recognize the presence of a pathogen, the signaling pathway is activated, resulti...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.12.019
更新日期：2018-01-25 00:00:00
abstract：:The goal of this study was to assess acetylcholinesterase (AChE) inhibition at different regions of the gastrointestinal (GI) tract following inhalation exposure to nerve agent sarin. Seven major regions of the GI tract were removed from saline control animals (n=3) and 677.4 mg/m(3) sarin-exposed animals at 4h (n=4) ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.03.011
更新日期：2010-09-06 00:00:00
abstract：:Neurotoxicity is a key dose-limiting factor for colistin therapy. This study aimed to investigate the protective effect of Salidroside on colistin-induced neurotoxicity in RSC96 Schwann cells and the underlying mechanisms. After Salidroside (12.5, 25, 50 μg/mL) treatment for 2 h, the cells were cultured with 250 μg/mL...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.04.027
更新日期：2017-06-01 00:00:00
