Abstract:
:Saikosaponin-d (SSd), one of the main constituents of the total saikosaponins extracted from Bupleurum falcatum L, possesses anti-inflammatory and anti-apoptosis effect. Recently, SSd was proved to improve depressive symptoms although exhibit hepatotoxicity in animals, but the central nervous system (CNS) toxicity of SSd remains unclear. The present study investigated the SSd-induced impairment in hippocampal cognitive function and explored the possible mechanisms involved. After intragastric administration of SSd (4mg/kg, 8mg/kg) for 7days, the learning and memory abilities of mice were evaluated by behavioral experiments. In the step-down passive avoidance test, we found that the mice treated with SSd showed a significant decrease of step-down latency and increase of the frequency of errors. In the Morris water maze task, both the escape latency and swimming distance of the mice treated with SSd were increased, correspondingly, both the time of mice staying in the target zone and the frequency of crossing platform were decreased. These neurobehavioral changes were accompanied by the reduction of the expression of 5-bromo-2'-deoxyuridine (BrdU), nestin, doublecortin (Dcx) and microtubule associated protein 2 (MAP2). Moreover, SSd significantly inhibited the expression of p-Akt, Foxg-1 and fibroblast growth factor 2 (FGF2) in the hippocampus of mice. These results indicated that SSd had a toxic effect on cognitive function in mice, which was associated with inhibiting the hippocampal neurogenesis via Akt/Foxg1 pathway.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Lixing X,Zhouye J,Liting G,Ruyi Z,Rong Q,Shiping Mdoi
10.1016/j.toxlet.2017.11.009subject
Has Abstractpub_date
2018-03-01 00:00:00pages
79-85eissn
0378-4274issn
1879-3169pii
S0378-4274(17)31457-1journal_volume
284pub_type
杂志文章abstract::This paper compares two methods for global optimization of physiologically based toxicokinetic models: Monte Carlo optimization, which searches randomly for the optimum; and the simplex method, which updates systematically an array of parameter values. Two measures of goodness-of-fit are also contrasted: criterion fun...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90103-5
更新日期:1993-08-01 00:00:00
abstract::DNA-damaging agents are commonly used as anticancer therapeutics. Unfortunately, such drugs induced DNA damages as well as DNA repair are important in mediating drug resistance to cancer treatments. To evaluate changes in DNA repair proteins that occur in DNA damage agent treatment, we challenged human A549 lung adeno...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.06.028
更新日期:2011-09-10 00:00:00
abstract::Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 +/- 15.8 micrograms nitrite/h X kg body wt. was detected between 5-24 h. Cerebral glutathione concentration was below the co...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90281-3
更新日期:1983-10-01 00:00:00
abstract::A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal ex...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.03.031
更新日期:2018-12-01 00:00:00
abstract::Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. However, in vivo studies in various, soman poisoned animal species showed a therapeutic effect of oximes, with the exac...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.10.005
更新日期:2018-09-01 00:00:00
abstract::Intraperitoneal injection of the iron-complex, ferric-nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage associated with oxidative damage in vivo. Fe-NTA induced a time-dependent decrease of several polyunsaturated fatty acids (PUFA), together with increased conjugated diene values and decreased cellula...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00372-1
更新日期:2001-09-15 00:00:00
abstract::Isolated, perfused and ventilated guinea-pig lungs were exposed for 10 min to acid (sulphuric + nitric acid) aerosol mimicking acid rain at pH 4.5 or 2.5, as well as to a control distilled water aerosol (pH 6.0-6.5). Lung perfusing solution was recovered and thromboxane (TX) B2 and leukotriene (LT) B4 were measured by...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90262-1
更新日期:1987-11-01 00:00:00
abstract::Toxicity of a compound for an organism is dependent on the route of exposure, the amount (or concentration), the way in which the compound is taken up, distributes and is eliminated from the organism (ADME, kinetics) and the intrinsic properties (reactivity; mode of action, dynamics) of the compound towards the organi...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(02)00367-3
更新日期:2003-02-18 00:00:00
abstract::Hsp90, p23 and other chaperosome proteins are critical for the function of several enzymes and steroid hormone receptors. The dioxin receptor (DR) is an Hsp90-regulated transcription factor that binds numerous toxic ligands, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo(p)dioxin. We used a yeast m...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00465-9
更新日期:2002-03-24 00:00:00
abstract::Bisphenol A (BPA) is a potential endocrine disruptor. It has been shown that it can interfere with steroid biosynthesis and metabolism. However, the mechanism is unclear. The objective of the present study is to investigate the effects of BPA on two isoforms of 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2)...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.10.002
更新日期:2012-11-30 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are ubiquitous environmental pollutants found in tobacco smoke, air pollution, and grilled foods. Reactive metabolites and reactive oxygen species generated during PAH metabolism are detoxified by reactions involving glutathione (GSH). Early life...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.11.017
更新日期:2014-10-15 00:00:00
abstract::3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows asse...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.10.005
更新日期:2012-01-05 00:00:00
abstract::Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00128-3
更新日期:1998-10-15 00:00:00
abstract::Polyhexamethylene guanidine (PHMG) phosphate is a competitive disinfectant with strong antibacterial activity. However, epidemiologists revealed that inhaled PHMG-phosphate may increase the risk of pulmonary fibrosis associated with inflammation, resulting in the deaths of many people, including infants and pregnant w...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.01.005
更新日期:2015-03-04 00:00:00
abstract::Aromatic amines are metabolically activated into mutagenic compounds by both animal and plant systems. The 4-nitro-o-phenylenediamine (NOP) is a well-known direct-acting mutagen whose mutagenic potential can be enhanced by plant metabolism; m-phenylenediamine (m-PDA) is converted to mutagenic products detected by the ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.05.011
更新日期:2004-11-02 00:00:00
abstract::Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and depletion of striatal dopamine (DA), leading to a range of motor symptoms, including resting tremor, rigidity, bradykinesia and postural abnormalities. The neurotoxin (MPTP) and its active metabol...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.03.003
更新日期:2013-05-23 00:00:00
abstract::We investigated the characteristics of hepatic cytochrome P450s and flavin-containing monooxygenase 1 (FMO1) in male Nts:Mini rats, a Wistar/Jcl-derived transgenic rat strain showing less plasma GH concentration than the parental strain. The total hepatic P450 contents of Mini rats were significantly reduced. A suppre...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(99)00055-7
更新日期:1999-06-01 00:00:00
abstract::Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 ppm or 85 ppm arsenic) from gestation da...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.12.016
更新日期:2012-03-07 00:00:00
abstract::Mercury, one of the widespread pollutants in the world, induces oxidative stress and dysfunction in many cell types. Alveolar type II epithelial cells are known to be vulnerable to oxidative stress. Alveolar type II epithelial cells produce and secrete surfactants to maintain morphological organization, biophysical fu...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.02.003
更新日期:2010-05-04 00:00:00
abstract::The incidence of spontaneous neoplasms in outbred, inbred and F1 hybrid strains was compared using the Charles River-CD rat and mouse, the F344 rat, and B6C3HF1 mouse. These strains are commonly used in carcinogenic studies. Each strain has a consistent pattern of tumor occurrence; testicular, pituitary and lymphoreti...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90113-8
更新日期:1982-04-01 00:00:00
abstract::A low-Mr copper (Cu) and zinc (Zn)-binding protein was present in the liver of a control water lizard Triturus pyrrhogaster. Cadmium (Cd) accumulated in the liver of the animals after intramuscular injections of Cd salt and was bound to Cu- and Zn-binding protein of a single isoform that had properties characteristic ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90203-0
更新日期:1984-05-01 00:00:00
abstract::Hepatic and renal microsomal electron transport components and erythrocyte delta-aminolevulinate dehydratase were investigated in adult male rats exposed to 0, 50, 200 and 600 ppm tetrachloroethylene for 4 weeks. Body weight and liver weight showed a significant decrease only in the 600 ppm group. A dose-dependent dec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90185-o
更新日期:1990-12-01 00:00:00
abstract::Mutagenic activity of aflatoxin B1 (AFB1) was followed in the Ames Salmonella/microsome test using liver S-9 from control and partially hepatectomized (PH) mice. The S-9 preparations from the PH mice were capable of inducing significantly greater AFB1 mutagenic activity to strain TA100 than S-9 preparations from eithe...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90060-1
更新日期:1982-12-01 00:00:00
abstract::Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is asso...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.12.006
更新日期:2013-03-13 00:00:00
abstract::Protein S-glutathionation has been demonstrated to be one of the cellular responses under oxidative stress and may be involved in many cellular metabolisms. In this study, the effect of redox cycling bipyridylium compounds, paraquat and diquat, on this protein modification was investigated. Male Sprague-Dawley rats we...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03621-0
更新日期:1996-02-01 00:00:00
abstract::Women over 50 years of age in 32 cadmium(Cd)-polluted and 16 nonpolluted hamlets were studied. Itai-itai disease patients and proteinuria with glucosuria were used as indices of the effect of Cd on health. Unpolished rice samples were collected from 568 households in the same area and analyzed for Cd. The hamlet's ave...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90236-9
更新日期:1983-07-01 00:00:00
abstract::Mice given single i.v. doses of some radiopharmaceuticals containing stannous chloride as a reducing agent, showed significant inhibition of hepatic azo-reductase and aromatic hydroxylase activity at dose levels which contained as little as 0.2 mg/kg of stannous chloride. Cytochrome P-450 content was also reduced sign...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90105-4
更新日期:1983-09-01 00:00:00
abstract::Spontaneous neoplasms in untreated control CD-1 mice (725 males and 725 females) used in carcinogenicity studies were evaluated and tabulated. The most common neoplasms in male mice were alveolar-bronchiolar adenomas (19.3%) followed by hepatocellular adenomas (11.0%), lymphoreticular neoplasms (6.8%), hepatocellular ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(92)90064-q
更新日期:1992-06-01 00:00:00
abstract::Many industrially and environmentally important industrial carcinogens display effects that lead them to be viewed and regulated as 'genotoxic compounds'. Some of these chemicals cause experimental tumours only at high or toxic doses. The current view is that non-threshold principles should be applied for risk assessm...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(02)00495-2
更新日期:2003-04-11 00:00:00
abstract::To investigate mechanisms of neuronal cell death in response to chlorpyrifos (CPF), a pesticide, we evaluated the regulation of ROS and COX-2 in human neuroblastoma SH-SY5Y cells treated with CPF. CPF treatment produced cytotoxic effects that appeared to involve an increase in ROS. In addition, CPF treatment activated...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.02.003
更新日期:2013-04-26 00:00:00