Abstract:
:The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate the hepatotoxicity mechanism of AE, the zebrafish Tg (fabp10: EGFP) was used as an animal model in vivo. The pathological sections of zebrafish liver were analyzed to observe the histopathological changes and Sudan black B was used to study whether there were inflammatory reactions in zebrafish liver or not. Then TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptotic signal of zebrafish liver cells, finally the mRNA expression levels as well as the protein expression levels of the targets in NF-κB and P53 pathways in zebrafish were measured by quantitative Real-Time PCR (qRT-PCR) and western blot. Molecular docking results showed that AE could successfully dock with all the targets of NF-κB and P53 pathways, and the docking scores of most of the targets were equal to or higher than that of the corresponding ligands. Pathological sections showed AE could cause zebrafish liver lesions and the result of Sudan black B staining revealed that AE blackened the liver of zebrafish with Sudan black B. Then TUNEL assay showed that a large number of dense apoptotic signals were observed in AE group, mainly distributed in the liver and yolk sac of zebrafish. The results of qRT-PCR and western blot showed that AE increased the mRNA and protein expression levels of pro-inflammatory and pro-apoptotic targets in NF-κB and P53 pathways. AE could activate the NF-κB inflammatory pathway and the P53 apoptosis pathway, and its hepatotoxic mechanism was related to activation of NF-κB-P53 inflammation-apoptosis pathways.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Quan Y,Gong L,He J,Zhou Y,Liu M,Cao Z,Li Y,Peng Cdoi
10.1016/j.toxlet.2019.02.007subject
Has Abstractpub_date
2019-05-15 00:00:00pages
66-79eissn
0378-4274issn
1879-3169pii
S0378-4274(18)32014-9journal_volume
306pub_type
杂志文章abstract::(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(98)00192-1
更新日期:1998-11-23 00:00:00
abstract::Subchronic oral toxicity of turmeric and ethanolic turmeric extract was studied in female Swiss mice and Wistar rats fed turmeric (0, 1 and 5%) and ethanolic turmeric extract (0, 0.05 and 0.25%) through diet for 14 and/or 90 days. The administration of a high dose of turmeric (5%) for longer duration (90 days) showed ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00035-6
更新日期:1998-05-01 00:00:00
abstract::A model of the growing small animal skeleton has been developed. The model accurately reproduces a variety of different kinds of measurements made at different ages in different species, as well as reproducing a precise and detailed series of measurements in the growing guinea pig. Of the multiple mechanisms responsib...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90022-7
更新日期:1988-10-01 00:00:00
abstract::Treatment of pregnant C57BL/6N mice with 2,3,7,8-tetrachlorodibenzofuran (TCDF) (0, 250, 500, and 1000 micrograms/kg on gestation day 10 or 0, 10, 30, 50, and 100 micrograms/kg on gestation days 10-13) results in dose-related increases in isolated cleft palates and hydronephrotic kidneys in the offspring. TCDF is tera...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90145-0
更新日期:1984-02-01 00:00:00
abstract::Oral administration of a single dose of dibutyltin dilaurate (DBTL, 80 mg/kg body wt.), 2 or 24 h after treatment, caused no significant change in the levels of diacylglycerol and phosphoinositides in rat cerebrum (forebrain), whereas daily administration of DBTL (40 or 80 mg/kg body wt.) for 3 days (24 h after the fi...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(91)90198-f
更新日期:1991-08-01 00:00:00
abstract::In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.05.020
更新日期:2017-07-05 00:00:00
abstract::Pregnant mice of C57BL/6 and DBA/2 inbred strains were exposed to cigarette smoke during days 1-18 of pregnancy. Both mothers and offspring were killed at the age of 21-22 weeks, and ovaries were studied with respect to the number of primordial follicles and small primary follicles. In additional studies, 7,12-dimethy...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90103-1
更新日期:1985-04-01 00:00:00
abstract::The hedgehog (HH) signaling pathway plays an important role in lung development, but its significance in silicosis is unclear. We showed that in human coal pneumoconiosis autopsy specimens, Sonic Hedgehog (SHH) and the Glioma-associated oncogene homolog transcription factors family (GLI) 1 proteins were up-regulated, ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.05.023
更新日期:2019-10-01 00:00:00
abstract::Nonylphenol (NP) is a representative endocrine disruptor that has an adverse effect on male reproduction and posses direct hazard to Sertoli cells, but the mechanism remains incompletely elucidated. In the present study, based on the structural comparability and high affinity between NP and membrane phospholipid molec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.08.011
更新日期:2008-12-15 00:00:00
abstract::PFAS are man-made compounds that are highly spread in the environment. Human dietary exposure to such contaminants is of high concern as they may accumulate in the food chain. Different studies already demonstrated the importance of the fish consumption in the dietary exposure of these molecules and the potential incr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.07.028
更新日期:2014-12-01 00:00:00
abstract::Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.04.015
更新日期:2009-08-10 00:00:00
abstract::Methoxetamine is one of the constantly growing group of novel psychoactive substances that has emerged in recent years. The compound belongs to the arylcyclohexylamine class, which is used for its recreational and psychedelic effects. Methoxetamine is a structural analogue of ketamine, with a much longer duration of a...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2014.08.011
更新日期:2014-11-04 00:00:00
abstract::Rats surviving various single dose of the organophosphorus anticholinesterase nerve agents Soman and Sarin were examined by light microscopy at intervals up to 35 days post-exposure. Brain lesions, identical to those that have been reported elsewhere were present, as well as a previously unreported finding associated ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90192-5
更新日期:1987-05-01 00:00:00
abstract::The present study was undertaken in an attempt to reconcile the seemingly conflicting observations that glutathione-dependent biotransformation of methyl parathion (O,O-dimethyl-O-(4-nitrophenyl)phosphorothionate) by hepatic supernatant or partially purified glutathione S-transferases occurs in vitro, but not to any s...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90018-s
更新日期:1993-06-01 00:00:00
abstract::In vivo administration of 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produced much higher hepatic microsomal aryl hydrocarbon hydroxylase (AHH) induction than 7,8-benzoflavone (7,8-BF) in both aromatic hydrocarbon (Ah)-responsive and nonresponsive strains of mice. Simultaneous treatment o...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90095-f
更新日期:1993-02-01 00:00:00
abstract::Coumarin and its derivatives are widely employed as a fragrance in cosmetics and skin care products. The skin absorption level and possible disruption to the skin by topical application of coumarins were evaluated in this study. Percutaneous absorption of osthole, daphnoretin, coumarin, byakangelicin, and 7-hydroxycou...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.02.009
更新日期:2014-04-21 00:00:00
abstract::In Europe and the USA the prevalence of certain forms of allergic disease is rising; an increase that can not be reconciled simply on the basis of changes in diagnostic fashion. The changes observed have been too rapid to be explained by alterations in the gene pool and, as a consequence, there has been a growing inte...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00320-8
更新日期:1998-12-28 00:00:00
abstract::The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(81)90016-3
更新日期:1981-12-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that induces apoptosis of neurons and a pro-inflammatory response in microglial cells. First, we found that TCDD induced proliferation of HAPI microglial cells in a dose- and time-dependent manner. Flow cytometry analysis showed that this proliferati...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.11.003
更新日期:2014-01-30 00:00:00
abstract::The effects of cytochrome P-450 inhibition by alpha-phenyl-alpha-propylbenzeneacetic acid 2-[diethylamino]-ethyl ester hydrochloride (SKF-525A), which inhibits the activity of a number of cytochrome P-450s, on triphenyltin metabolism and toxicity in mice were studied. At 24 h after triphenyltin administration, the tri...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00255-1
更新日期:2000-11-20 00:00:00
abstract::The effects of vitamin C on acute paracetamol poisoning were studied in mice. Given orally at 50, 100 or 200 mg/kg, either simultaneously or 2 h after the oral administration of 875 mg/kg of paracetamol, vitamin C did not cause any decrease in the mortality rate. In similar conditions in previous experiments methionin...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90086-3
更新日期:1983-08-01 00:00:00
abstract::Nuclear accumulation of the tumorsuppressor protein p53 indicates the occurrence of chromatin injury (J. Cancer Res. Clin. Oncol. 1991, 117, 30; Oncogene 1993, 8, 307) and may be used as an analytical tool to detect genotoxic agents. This mechanism was used to evaluate the DNA-damaging potency (clastogenicity) of the ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(96)03711-3
更新日期:1996-11-01 00:00:00
abstract::Pneumotoxicity of butylated hydroxytoluene (BHT) applied to the skin of CD-1 mice was investigated and compared with that of butylated hydroxyanisole (BHA). To 6 groups of 10 male mice and 10 female mice 0.1 ml of dimethylsulfoxide (DMSO) solutions containing 0, 5, 10, 20, or 30 mg of BHT or 30 mg of BHA were topicall...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90151-7
更新日期:1986-11-01 00:00:00
abstract::The adverse effects on the immune system resulting from acute and subchronic exposure to immunotoxic compounds can be divided into the following three categories. One is the tissue manifestations induced by either immunosuppressive or immunomodulative compounds through the interactions of the drug or its metabolites w...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(92)90177-l
更新日期:1992-12-01 00:00:00
abstract::Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, acc...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.10.006
更新日期:2012-12-17 00:00:00
abstract::Fine particulate matter 2.5 (PM2.5), one of the main components of air pollutants, seriously threatens human health. Possible neuronal dysfunction induced by PM2.5 has received extensive attention. However, there is little evidence for the specific biochemical mechanism of neuronal injury induced by PM2.5. Moreover, t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.06.014
更新日期:2020-10-01 00:00:00
abstract::Polybrominated diphenyl ethers (PBDEs) are widespread environmental pollutants, and the levels of certain congeners have been increasing in biota and abiota in recent decades. Some PBDEs are lipophilic and persistent, resulting in bioaccumulation in the environment. Their structural similarity to other polyhalogenated...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.12.002
更新日期:2006-07-01 00:00:00
abstract::Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.03.013
更新日期:2013-06-07 00:00:00
abstract::N-(3,5-Dichlorophenyl)succinimide (NDPS) induces nephrotoxicity via one or more metabolites which arise from oxidation of the succinimide ring. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3-NDHSA), a potential metabolite of NDPS and a positiona...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90047-7
更新日期:1989-09-01 00:00:00
abstract::In this study we evaluated the rat Leydig cell carcinoma cell line R2C and the human adrenocorticocarcinoma cell line H295R for their suitability as in vitro screening tools for potential interference of xenobiotics with aromatase activity. A 24h exposure to prochloraz (PRO), fadrozole (FAD) and epoxyconazole (EPO) re...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.10.002
更新日期:2004-01-15 00:00:00