Abstract:
:Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood-brain barrier. Our previous works show that bile duct ligation (BDL) impairs expression and function of brain BCRP in rats. Since zidovudine (AZT) is BCRP substrate, we investigated whether impaired expression and function of BCRP increased brain distribution and toxicity of AZT in BDL-D7 rats. After administration of AZT (10 mg/kg, i.v.), BDL markedly increased brain AZT concentrations, compared with sham-operated (SO) rats. The ratio of AZT brain-to-plasma area under concentration curve (AUC) in BDL rats was increased to 1.6-folds of SO rats. After treatment with AZT (100 mg/kg every day, i.v.) for 7 days, BDL significantly impaired cognitive functions compared with SO rats, evidenced by the significantly decreased percentage of alternation in Y-maze test and prolonged escaped latency in two-way passive avoidance trial. Furthermore, AZT treatment caused significant decrease in copies of mitochondrial DNA and mitochondrial membrane potential in hippocampus of BDL rats. Moreover, AZT treatment caused a significant decrease of cortex microtubule-associated protein 2 and hippocampus synaptophysin levels in BDL rats. AZT-induced CNS adverse alterations in BDL rats were not observed in SO rats treated with AZT. In conclusion, BDL decreases the function and expression of brain BCRP in rats, leading to increased brain distribution of AZT, which in turn enhances AZT CNS toxicity, leading to mitochondrial dysfunction, neuronal damage, and ultimately cognitive dysfunction.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Qin YY,Xu P,Wu T,Qian CQ,Fan YL,Gen DH,Zhu L,Kong WM,Yang HY,Xu F,Yang YT,Liu L,Liu XDdoi
10.1038/s41401-019-0242-8subject
Has Abstractpub_date
2020-02-01 00:00:00pages
181-191issue
2eissn
1671-4083issn
1745-7254pii
10.1038/s41401-019-0242-8journal_volume
41pub_type
杂志文章abstract::Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies. During human multistep hepatocarcinogenesis, genomic gain represents an important mechanism in the activation of proto-oncogenes. In many circumstances, activated oncogenes hold clinical implications both as prognostic markers and targets f...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2010.94
更新日期:2010-09-01 00:00:00
abstract:AIM:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). METHODS:The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2008.18
更新日期:2009-02-01 00:00:00
abstract::DJ-1 is a multifunctional protein associated with cancers and autosomal early-onset Parkinson disease. Besides the well-documented antioxidative stress activity, recent studies show that DJ-1 has deglycation enzymatic activity and anti-ferroptosis effect. It has been shown that DJ-1 forms the homodimerization, which d...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00531-1
更新日期:2020-10-06 00:00:00
abstract:AIM:To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. METHODS:Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoass...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract:AIM:The changes of seizure susceptibility of transgenic mice overexpressing GABA transporter-1 (GAT-1) were studied to clarify the possible role of GABAergic transmission in epileptogenesis. METHODS:Seizures were induced by intraperitoneal administration of pentylenetetrazol (PTZ), picrotoxin (PIC), or kainic acid (KA...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract:AIM:To investigate the blood pressure (BP), baroreflex sensitivity (BRS), and organ damage in hybrids of spontaneously hypertensive rats and Sprague-Dawley rats. METHODS:Spontaneously hypertensive rats and Sprague-Dawley rats were crossbred, and the F1 hybrids were inbred randomly to produce an F2 generation. At the a...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00162.x
更新日期:2005-09-01 00:00:00
abstract::Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-018-0086-7
更新日期:2018-12-01 00:00:00
abstract:AIM:To study whether etodolac enantiomers have pharmacokinetic difference after oral administration. METHODS:Fourteen rats, divided into two groups randomly, were orally given S-(+)- or R-(-)-etodolac at a single dose of 20 mg/kg, respectively. Blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract::Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0303-z
更新日期:2020-03-01 00:00:00
abstract:AIM:The aim of this study was to design and synthesize a series of high activity compounds against aspartyl protease beta-secretase (BACE-1) bearing hydroxyethylene (HE) framework. METHODS:First, we designed the small library based on our previous work and rational analysis. Subsequently, thirteen compounds were selec...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2008.26
更新日期:2009-02-01 00:00:00
abstract:AIM:To investigate the proliferation of vascular smooth muscle cells (VSMC) affected by ginsenoside Rg1 and further explore the molecular mechanism of ginsenoside Rg1 using proteomics. METHODS:The proliferation of VSMC was measured by MTS assay kit and flow cytometry. Proteomic alterations were analyzed using two-dime...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00331.x
更新日期:2006-08-01 00:00:00
abstract:AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2015.73
更新日期:2015-10-01 00:00:00
abstract:AIM:Radiation-induced brain injury (RIBI) is the most common and severe adverse effect induced by cranial radiation therapy (CRT). In the present study, we examined the effects of the traditional Chinese medicine Shenqi Fuzheng Injection (SFI) on RIBI in mice, and explored the underlying mechanisms. METHODS:C57BL/6J m...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.69
更新日期:2015-11-01 00:00:00
abstract:AIM:To study the effect of semi-synthesized quercetin water-soluble derivatives sodium quercetin-7-sulfate (SQMS) and disodium quercetin-7,4 -disulfate (SQDS) on recombinant human phosphatidylinositol 3-kinase (PI3-K) p110 beta catalytic subunit. METHODS:Recombinant human PI3-K p110 beta catalytic subunit was expresse...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Pulmonary fibrosis may be partially the result of deregulated tissue repair in response to chronic hypoxia. In this study we explored the effects of hypoxia on lung fibroblasts and the effects of neotuberostemonine (NTS), a natural alkaloid isolated from Stemona tuberosa, on activation of fibroblasts in vitro and in v...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.202
更新日期:2018-09-01 00:00:00
abstract:AIM:To study the effect of nociceptin (orphanin FQ), a newly discovered heptadecapeptide, on cholinergic constrictions in isolated trachea and bronchus of rat. METHODS:The electric field stimulation (EFS) induced a monophasic constriction, which was due to an activation of the cholinergic nerves. RESULTS:Nociceptin 0...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::Cancer metastasis is responsible for over 90% of breast cancer-related deaths, and inhibiting lymph node metastasis is an option to treat metastatic disease. Herein, we report the use of IR-780-loaded polymeric micelles (IPMs) for effective photothermal therapy (PTT) of breast cancer lymphatic metastasis. The IPMs wer...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.109
更新日期:2018-01-01 00:00:00
abstract:AIM:Tolsultazolamide, a novel carbonic anhydrase inhibitor, is designed for the prophylaxis and treatment of acute mountain sickness. The aim of this study was to investigate the pharmacokinetics, tissue distribution, and excretion characteristics of tolsultazolamide and the sex difference in pharmacokinetics in rats. ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.146
更新日期:2014-02-01 00:00:00
abstract:AIM:To examine the stimulatory effect of bacille Calmette-Gu rin (BCG) cell wall components on human beta-defensin-1 (hBD-1) gene expression and analyze the response element in the 5'-flanking region of the gene. METHODS:BCG cell wall proteins were fractionated by Sephadex G-150 chromatography. Using reverse-transcrip...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor impairment and progressive loss of dopamine (DA) neurons. At present, the acute application of neurotoxic drugs such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are commonly used to simulate ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0379-5
更新日期:2020-04-01 00:00:00
abstract:AIM:The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remo...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.22
更新日期:2016-06-01 00:00:00
abstract:AIM:Gemcitabine has been increasingly prescribed for the treatment of gallbladder cancer. However, the response rate is low. The aim of this study is to determine whether icariin, a flavonoid isolated from Epimedi herba, could potentiate the antitumor activity of gemcitabine in gallbladder cancer. METHODS:Human gallbl...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.162
更新日期:2013-02-01 00:00:00
abstract:AIM:To study the effect of Huangqi Jianzhong Tang in reducing fatigue improvement in athletes. METHODS:Twelve athletes were randomly separated into a control group, whose members were administered with placebos, and the experimental group, whose members were administered with Huangqi Jianzhong Tang. During the eight w...
journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-08-01 00:00:00
abstract::KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gli...
journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:10.1038/aps.2016.103
更新日期:2017-01-01 00:00:00
abstract::Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a prot...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0462-y
更新日期:2020-10-01 00:00:00
abstract:AIM:Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.47
更新日期:2015-08-01 00:00:00
abstract:AIM:To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. METHODS:Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00828.x
更新日期:2008-08-01 00:00:00
abstract::Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-018-0066-y
更新日期:2019-01-01 00:00:00
abstract::Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). W...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.51
更新日期:2009-06-01 00:00:00