Abstract：
:Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of doxorubicin (DOX) as an anti-tumoral drug, but the mechanism of DOX-mediated apoptosis remains unclear. We examined the interplay between oxidative stress and cell death in cardiac-derived H9c2 myocytes exposed to DOX doses in the range of the plasma levels found in patients undergoing chemotherapy. A low DOX concentration (0.25 microM) induced apoptosis, whereas the cells treated with the high dose of 2 microM also showed necrosis. The production of reactive oxygen species (ROS) and induction of oxidative stress markers was increased in the cells treated with 2 microM DOX but not in those treated with the low dose. Surprisingly, heme oxygenase (HO-1) expression was down-modulated in the cells exposed to 0.25 microM DOX, and its Bach 1 transcriptional repressor was induced. In line with the role of HO-1 as an anti-apoptotic protein, inhibiting HO-1 activity with SnPPIX was sufficient to induce apoptosis and increased DOX-mediated apoptosis, whereas hemin-induced HO-1 activation prevented DOX-mediated apoptotic cell death. In brief, our findings do not support the hypothesis that oxidative stress plays a role in the apoptotic cell death occurring in cardiomyocytes exposed to low concentrations of DOX, but suggest that DOX may facilitate the apoptosis of cardiomyocytes by inhibiting the anti-apoptotic HO-1.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Bernuzzi F,Recalcati S,Alberghini A,Cairo Gdoi
10.1016/j.cbi.2008.09.012subject
Has Abstractpub_date
2009-01-15 00:00:00pages
12-20issue
1eissn
0009-2797issn
1872-7786pii
S0009-2797(08)00497-3journal_volume
177pub_type
杂志文章abstract：:The uptake and binding of ring-labelled [-14C]aflatoxin B1 (AFB1) by rat and hamster liver and kidney has been studied, the former species being extremely sensitive to the carcinogenic action of AFB, whereas the latter is resistant. In contrast to an earlier report (Lijinsky et al, Cancer Res., 30 (1970) 2280-2283, b...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(75)90019-8
更新日期：1975-08-01 00:00:00
abstract：:The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the adaptation and proliferation of tumor cells; therefore HIF-1 has become an important target in the development of anticancer drugs. Dihydrotanshinone I (DHTS) is a phenanthrenequinone compound from Salvia miltiorrhiza Bunge, which has been u...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.08.006
更新日期：2015-10-05 00:00:00
abstract：:Polyphenols, coumarin (1,2-benzopyrone) and chromone (1,4-benzopyrone), are naturally occurring constituent of variety of plant species. They have attracted immense interest because of their diverse pharmacological activities. Not much was known about biological activities of acetyl derivative (polyphenolic acetates) ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.02.025
更新日期：2010-05-14 00:00:00
abstract：:Parthenolide (PTL), a well-known sesquiterpene lactone of natural origin with α,β-unsaturated carbonyl structure, has proven to show promising anti-cancer properties. In this report, anti-proliferative potential of two synthetic methyleneisoxazolidin-5-ones, MZ-6 and MZ-14, with the same structural motif, has been inv...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.01.011
更新日期：2016-03-25 00:00:00
abstract：:Little is known about the roles of aldehyde dehydrogenases in non-vertebrate animals. We recently showed that in Drosophila melanogaster, an enzyme with ∼70% amino acid identity to mammalian ALDH2 is necessary for detoxification of dietary ethanol. To investigate other functions of this enzyme, DmALDH, encoded by the ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.01.031
更新日期：2011-05-30 00:00:00
abstract：:2,4,6-Triphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2В in rats. Several analogs of TPD were synthesized to verify a hypothesis that minor changes in the inducer structure can cause changes in induction abilities (R=H, cisTPD and transTPD; R=N(CH(3))(2), transpDMA; R=NO(2), transpNO(2)...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.03.005
更新日期：2011-07-15 00:00:00
abstract：:Obesity is characterized by the deposition of excessive body fat, and is caused by energy imbalance, especially when consuming fat-rich diets. High fat diet (HFD)-associated obesity is greatly common in patients with non-alcoholic fatty liver disease (NAFLD) that is emerging as one of the most universal causes of live...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2020.109199
更新日期：2020-10-01 00:00:00
abstract：:To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-b...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(88)90026-9
更新日期：1988-01-01 00:00:00
abstract：:Bitumens contain traces of polycyclic aromatic compounds (PACs), a part of which will end up in the fumes emitted during hot handling of bitumen-containing products, e.g. during roadpaving. Although exposure of workers to these fumes is low, it might lead to health problems. Studies on bitumen fume condensates (BFCs) ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(96)03705-2
更新日期：1996-08-14 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：:The metabolism of [3H]benzo[a]pyrene (BP) and (-)-trans-[14C]7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was studied in freshly isolated hepatocytes of the wild benthic fish, brown bullhead (Ictalurus nebulosus). Bullhead hepatocytes incubated with 40 microM [3H]BP for 1 h metabolized BP to water soluble met...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(90)90063-s
更新日期：1990-01-01 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：:Trypan blue at 50 microgram/ml stimulates the pinocytic uptake of 125I-labelled PVP, but not of colloidal 198Au or formaldehyde-denatured 125I-labelled bovine serum albumin, by the 17.5-day rat visceral yolk sac incubated in vitro. Neither Trypan blue nor a combination of the dye with 125I-labelled PVP stimulated the ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90097-6
更新日期：1980-11-01 00:00:00
abstract：:The asymmetric A12 acetylcholinesterase (AChE) molecular form, consisting of three tetrameric catalytic oligomers and three non-catalytic subunits of collagen Q (ColQ), is the functional AChE form in the neuromuscular junction. Its extremely high concentration and sharp localization in the junction is mostly due to th...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.008
更新日期：2005-12-15 00:00:00
abstract：:4-Methylcyclophosphamide, an analogue of the antitumour agent cyclophosphamide, exists in cis and trans forms, each of which comprises a pair of optical isomers. The extents of metabolism by rat liver microsomes during 20 min were compared for the four steroisomers incubated separately, and for the racemic cis and tra...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(77)90140-5
更新日期：1977-07-01 00:00:00
abstract：:The objectives of the present work were to study the effects of certain peroxisome proliferators on xenobiotic-metabolizing enzyme activities in the testes of normal and hypothyroid rats, i.e. phenol sulfotransferases (pST), phenol UDP-glucuronosyl transferases (pUDPGT), glutathione transferases (GST), catalase, epoxi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00020-3
更新日期：1997-05-02 00:00:00
abstract：:The genome of Escherichia coli K12 contains 9 open reading frames encoding aldo/keto reductases (AKRs) that are differentially regulated and sequence diverse. A significant amount of data is available for the E. coli AKRs through the availability of gene knockouts and gene expression studies, which adds to the biochem...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.10.008
更新日期：2013-02-25 00:00:00
abstract：:Human foreskin cell cultures in scheduled DNA synthesis (S phase) of the cell cycle were exposed to UV irradiation at a dose of 10 J . m-1 in the presence of insulin. These treated cell populations, when selectively passaged in a high amino acid supplemented complete growth medium (CM) after 20 Dulbecco's phosphate bu...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90028-4
更新日期：1981-07-01 00:00:00
abstract：:The neuropathologic mechanisms after exposure to lethal doses of nerve agent are complex and involve multiple biochemical pathways. Effective treatment requires drugs that can simultaneously protect by reversible binding to the acetylcholinesterase (AChE) and blocking cascades of seizure related brain damage, inflamma...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.10.016
更新日期：2013-03-25 00:00:00
abstract：:A new analysis of the quantitative structure-activity relationship (QSAR) of the antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse toxicity is reported. QSAR have also been derived for the inhibitory activity of the anilinoacridines with tumor cells and their binding to DNA. These results...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(98)00085-4
更新日期：1998-11-27 00:00:00
abstract：:The carcinogenic activity of the synthetic estrogen hexestrol was measured in male Syrian hamsters. Between 90% and 100% of the animals treated with hexestrol or with 3',3",5',5"-tetradeuteriohexestrol, implanted subcutaneously as 25-mg pellets, were found with renal carcinoma after 6-7 months. In vitro hexestrol meta...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(85)80125-3
更新日期：1985-10-01 00:00:00
abstract：:tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect at low doses, but is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (TBQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-t...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.09.023
更新日期：2015-06-05 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：:Susceptibility to drug toxicity is influenced by a variety of factors, both genetic and environmental. The focus of this article is the evidence addressing the hypothesis that inflammation is both a result of and a susceptibility factor for drug toxicity, with an emphasis on liver as a target organ. Results of studies...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2004.09.002
更新日期：2004-11-01 00:00:00
abstract：:The organ specificity of tris(2,3-dibromopropyl)phosphate(Tris-BP)-induced DNA damage was investigated in the rat 2 h after a single i.p. injection of 350 mumol/kg. Extensive DNA damage, measured with the alkaline elution method, was found in the kidney, liver and small intestine. Less, but significant DNA damage was ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90110-7
更新日期：1992-04-15 00:00:00
abstract：:Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and th...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.108863
更新日期：2020-01-05 00:00:00
abstract：:The characterization of the metabolic pathways of new chemical entities with a special emphasis on detecting potentially reactive metabolites is increasingly being performed early in the drug discovery process. In the present study, the preliminary in vitro metabolic routes of a series of novel 2-substituted benzothio...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.01.005
更新日期：2005-02-28 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：:Colon epithelium is made up of two general classes of cells, surface cells which are post-mitotic and crypt cells which contain the proliferative population. Their relative vulnerability to environmental damage and ability to perform DNA repair are important issues in colon carcinogenesis. DNA damage and repair was st...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(85)90026-2
更新日期：1985-01-01 00:00:00
abstract：:Many flavonoids have been shown to present good results for the treatment of gastric ulcers. Baicalein, a bioactive flavonoid derived from the Scutellaria baicalensis Georgi root, possesses several biological effects, such as anti-inflammatory and antioxidant. This study was conducted to assess the gastroprotective pr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.10.016
更新日期：2016-12-25 00:00:00
