Abstract：
:Hepatic injury remains not only the commonest reason for the termination of drugs in their pre-clinical development but is also the most frequent reason for the withdrawal of approved drugs from the market. Mitochondria are the central point where the different signals responsible for initiating hepatocyte cell death converge, irrespective of whether the cells ultimately die by apoptosis, necrosis (oncosis) or autophagic cell death. These signals can be in the form of direct damage to the mitochondria leading to permeability transition or can act indirectly through activation of death receptors and downstream pro-apoptotic Bcl-2 family proteins. This paper reviews our current knowledge about how hepatotoxic drugs, whether direct acting or through induction of steatosis or cholestasis, target mitochondria and cause hepatic injury.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Kass GEdoi
10.1016/j.cbi.2006.06.007subject
Has Abstractpub_date
2006-10-27 00:00:00pages
145-59issue
1-2eissn
0009-2797issn
1872-7786pii
S0009-2797(06)00147-5journal_volume
163pub_type
杂志文章,评审abstract：:A single dose of the carcinogen aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly enhanced the hepatic activity of protein kinase C in the particulate and nuclear fractions. The particulate fraction showed stimulation at 4 and 7 h, while the nuclear activity was increased at 17 h following administr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(96)03698-8
更新日期：1996-03-25 00:00:00
abstract：:The monoterpene β-myrcene has been widely used in cosmetics, food and beverages, and it is normally found in essential oil from citrus fruit. The aim of this study was to investigate the anti-ulcer effects of β-myrcene on experimental models of ulcers that are induced by ethanol, NSAIDs (non-steroidal anti-inflammator...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.01.009
更新日期：2014-04-05 00:00:00
abstract：:Carbonyl reductase (CR) is an enzyme which can catalyze the oxidoreduction of various carbonyl compounds in the presence of NAD(P)H. With the PCR method, using primers carrying the conserved nucleotide sequence among mammalian CRs, we isolated three different cDNAs (CHCR1, CHCR2 and CHCR3) which encode a unique carbon...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00240-4
更新日期：2001-01-30 00:00:00
abstract：:Alkyl adducts at the O6-position of guanine constitute promutagenic DNA lesions likely to be involved in the initiation of malignant transformation. They can be removed by a cellular acceptor protein termed O6-alkylguanine-DNA alkyltransferase (AT). In rat liver this repair enzyme can be induced by a variety of hepato...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(86)90060-8
更新日期：1986-12-01 00:00:00
abstract：:4-Hydroxy-2-nonenal (HNE), a major reactive product of lipid peroxidation, is believed to play a central role in atherogenic actions triggered by oxidized lipoproteins. An aldo-keto reductase (AKR) 1C15 efficiently reduces HNE and is distributed in many rat tissues including endothelial cells. In this study, we invest...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.12.018
更新日期：2011-05-30 00:00:00
abstract：:Anthracyclines (ANTs) are widely used in the treatment of various forms of cancer. Although their usage contributes to an improvement in life expectancy, it is limited by severe adverse effects-acute and chronic cardiotoxicity. Several enzymes from both AKR and SDR superfamilies have been reported as participants in t...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.12.016
更新日期：2011-05-30 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：:2-Hydroxy-3',5,5'-trimethoxychalcone (named DK-139) is a synthetic chalcone derivative that has anti-inflammatory, anti-tumor, and endoplasmic reticulum-mediated apoptosis activities. However, the mode of action of DK-139 on reactive oxygen species (ROS)-induced apoptosis remains unknown. In this study, we found that ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.11.003
更新日期：2019-01-25 00:00:00
abstract：:The ability of pantoprazole to affect the induction of cytochrome P450 (CYP) 1A subfamily was evaluated and compared with two other proton pump inhibitors, omeprazole and lansoprazole, in primary cultured hepatocytes from female Sprague-Dawley rats. The hepatocytes were cultured for 2 days, followed by treatment for 2...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00074-4
更新日期：1997-11-06 00:00:00
abstract：:The role of catecholamines in the toxicity of MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) was explored. The killing of cultured hepatocytes by dopamine and 6-hydroxydopamine was enhanced following inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a manipulation known to sensi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(93)90092-d
更新日期：1993-09-01 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：:MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to "mang...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.07.020
更新日期：2018-09-25 00:00:00
abstract：:The antioxidant mechanism of ebselen in rats brain is largely linked with its glutathione peroxidase (GPx) rather than its peroxiredoxin mimicry ability. However, the precise molecular dynamics between the GPx-mimicry of ebselen and thiol utilization is yet to be fully clarified and thus still open. Herein, we investi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.07.014
更新日期：2013-10-25 00:00:00
abstract：:Damage of cell membranes by reactive oxygen species results in the formation of toxic lipid peroxides which may ultimately lead to cell death. Among the best characterized intermediates of oxidative stress are the unsaturated aldehydes 4-hydroxynon-2-enal (4-HNE) and its oxidized counterpart 4-oxonon-2-enal (4-ONE). 4...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.10.021
更新日期：2009-03-16 00:00:00
abstract：:In a preliminary study screening anti-proliferative natural alkaloids, a very potent benzophenanthridine, chelidonine showed strong cytotoxicity in cancer cells. While several modes of death have been identified, most of anti-cancer attempts have focused on stimulation of cells to undergo apoptosis. Chelidonine seems ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.09.013
更新日期：2014-11-05 00:00:00
abstract：:Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypert...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(75)90087-3
更新日期：1975-04-01 00:00:00
abstract：:The aim of this study was to evaluate the effects of organosulfurs, isothiocyanates and vitamin C towards hydrogen peroxide-induced DNA damage (DNA strand breaks and oxidized purines/pyrimidines) in human hepatoma cells (HepG2), using the Comet assay. Treatment with hydrogen peroxide (H(2)O(2)) increased the levels of...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2007.05.006
更新日期：2007-08-15 00:00:00
abstract：:Tamoxifen, widely used as adjuvant therapy in the treatment of breast cancer, is now undergoing trials as a cancer chemopreventative agent. Previous work has shown an association between 32P-postlabelled adducts in rat liver DNA and the development of liver tumours. With the use of accelerator mass spectrometry, [14C]...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00063-x
更新日期：1997-09-12 00:00:00
abstract：:The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Previous studies have reported polyphosphate (PolyP)-mediated vascular inflammatory responses such as disruption of vascular integrity. Dabrafenib is a B-Raf...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.07.024
更新日期：2016-08-25 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
abstract：:Methylglyoxal (MGO), a cytotoxic metabolite, is produced from glycolysis. Elevated levels of MGO are observed in a number of diabetic complications, including retinopathy, nephropathy and cardiomyopathy. Loss of retinal pericyte, a hallmark of early diabetic retinal changes, leads to the development of formation of mi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.07.002
更新日期：2010-10-06 00:00:00
abstract：:The enzymatic oxidation of tetrachloro-1,4-hydroquinone (1,4-TCHQ), resulting in covalent binding to protein of tetrachloro-1,4-benzoquinone (1,4-TCBQ), was investigated, with special attention to the involvement of cytochrome P-450 and reactive oxygen species. 1,4-TCBQ itself reacted very rapidly and extensively with...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(88)90110-x
更新日期：1988-01-01 00:00:00
abstract：:A natural ursolic compound, 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidia chinensis Planch (A. chinensis Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to in...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.06.038
更新日期：2015-10-05 00:00:00
abstract：:ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase) is the enzyme in folate metabolism commonly downregulated in human cancers. One of the mechanisms of the enzyme downregulation is methylation of the promoter of the ALDH1L1 gene. Recent studies underscored ALDH1L1 as a candidate tumor suppressor and potential...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2019.02.013
更新日期：2019-04-01 00:00:00
abstract：:Dimethylnitrosamine (DMN) is a potent hepatotoxic, carcinogenic and mutagenic compound. It induces massive liver cell necrosis and death in experimental animals. Several drugs have been tested in the past for their protective behavior against DMN toxicity. However, it is for the first time that therapeutic interventio...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.10.009
更新日期：2018-11-01 00:00:00
abstract：:Aspirin is one of the oldest drugs and has been purported to have multiple beneficial effects, including prevention of cardiovascular disease and cancer, in addition to its original indication for treatment of inflammation, fever and pain. In cancer chemoprevention studies using animal models, two methods of aspirin a...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.10.008
更新日期：2009-05-15 00:00:00
abstract：:Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidan...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.12.005
更新日期：2012-01-25 00:00:00
abstract：:Variable temperature 1H-nuclear magnetic resonance (NMR) has been used to study the interaction of the RNA trimer, GpCpA, with the intercalators ethidium bromide and the acridine derivatives; proflavin, 9-amino-acridine, acridine orange, acridine yellow and acriflavin. The complexes formed were studied at nucleic acid...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(84)90135-2
更新日期：1984-06-01 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：:Copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, was removed with ammonium tetrathiomolybdate (TTM), and the fate of the Cu complexed with TTM and mobilized from the liver was determined. TTM ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00159-3
更新日期：2000-02-01 00:00:00
