Pharmacokinetic Characterization of Dehydroevodiamine in the Rat Brain

Ahn, Sung‐Hoon; Jeon, Seng‐Ho; Tsuruo, Takashi; Shim, Chang‐Koo; Chung, Suk‐Jae

doi:10.1002/jps.10546

Cited by 17 publications

(16 citation statements)

References 17 publications

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“…Table 2 summarizes the kinetic parameters for CsA transport to the brain. Whereas the brain-to-plasma concentration ratio for mannitol, a substance that is not permeable to the BBB (Ahn et al, 2004), was not affected (i.e., 40.6 Ϯ 1.84 versus 39.8 Ϯ 1.21 l/g brain for control versus diabetic rats, respectively), the concentration ratio for CsA was significantly reduced in the diabetic rats (37.5 Ϯ 7.43 l/g brain), compared with the control rats (56.9 Ϯ 5.66 l/g brain). In addition, the apparent brain uptake clearance by integration plot analysis (Kusuhara et al, 1997) was also reduced by the induction of diabetes (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…at ASPET Journals on May 10, 2018 dmd.aspetjournals.org the underlying mechanism for the enhanced expression and the function of P-glycoprotein, MBEC4 cells, an in vitro model of the BBB (Ahn et al, 2004), was used. The level of NO x generated from 1 mM NO x donors in the cell culture condition is summarized in Table 3.…”

Section: Functional Induction Of P-gp In Stz-induced Diabetic Ratsmentioning

confidence: 99%

“…The current study, therefore, was undertaken to investigate the underlying mechanism for the functional alteration of P-glycoprotein in the BBB of the STZ-induced diabetic rats and an in vitro model of the BBB [viz., MBEC4 cells (Tatsuta et al, 1992;Ahn et al, 2004)] pretreated with NO x donors. Since diabetes is known to produce a nitrosative stress condition and the exposure of NO x may lead to a regulation of the gene expression of efflux transporters (Heemskerk et al, 2007), the role of NO x in the functional alteration of P-glycoprotein in the BBB was of particular interest.…”

mentioning

confidence: 99%

“…For this study, MBEC4 cells, immortalized mouse brain capillary endothelial cells (Tatsuta et al, 1992), were used as an in vitro model of the BBB. Standard protocols were used for subculturing in a T-flask and seeding in 12-well culture plates (Ahn et al, 2004). Cells were maintained at 37°C in Dulbecco's modified Eagle's medium (low glucose), 10% fetal bovine serum, 1% nonessential amino acid solution, 100 units/ml penicillin, and 0.1 mg/ml streptomycin in an atmosphere of 5% CO 2 and 90% relative humidity.…”

mentioning

confidence: 99%

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Functional Induction of P-glycoprotein in the Blood-Brain Barrier of Streptozotocin-Induced Diabetic Rats: Evidence for the Involvement of Nuclear Factor-κB, a Nitrosative Stress-Sensitive Transcription Factor, in the Regulation

Maeng¹,

Kim²,

Jin³

et al. 2007

Drug Metab Dispos

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ABSTRACT:The objective of this study was to investigate the transport kinetics of cyclosporin A, a well known substrate for P-glycoprotein (P-gp), across the blood-brain barrier (BBB), and the expression of the transporter in the brain of streptozotocin-induced diabetic rats. The in vivo transport clearance of cyclosporin A was significantly reduced in diabetic rats compared with that in the control.

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Section: Resultsmentioning

confidence: 99%

Section: Functional Induction Of P-gp In Stz-induced Diabetic Ratsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Functional Induction of P-glycoprotein in the Blood-Brain Barrier of Streptozotocin-Induced Diabetic Rats: Evidence for the Involvement of Nuclear Factor-κB, a Nitrosative Stress-Sensitive Transcription Factor, in the Regulation

Maeng¹,

Kim²,

Jin³

et al. 2007

Drug Metab Dispos

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“…As DHED is easy to pass through the blood-brain barrier and has been reported to have the least side-effects and the lowest dosing among the cholinesterase inhibitors [9,10,30] , in addition to the present findings, it may be a promising candidate for the drug development of AD. …”

Section: Discussionmentioning

confidence: 72%

Dehydroevodiamine attenuates calyculin A-induced tau hyperphos-phorylation in rat brain slices

Fang

Tian

et al. 2007

Acta Pharmacol Sin

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Aim: This study was to investigate the effect of dehydroevodiamine (DHED) on Alzheimer's disease (AD)-like tau hyperphosphorylation induced by calyculin A (CA), an inhibitor of protein phosphatase (PP)-2A and PP-1, and the involvement of PP-2A in metabolically competent rat brain slices. Methods: Rat brain slices were pre-incubated at 33 °C in the presence (10, 100, and 200 µmol/L, respectively) or absence of DHED for 1 h. Then, CA 0.1 µmol/L was added and the slices were treated for another 2 h. Western blotting and/or immunohistochemistry were used to measure the phosphorylation level of tau and PP-2A. Results: CA treatment could remarkably increase the immunoreactivity of pS262 and decrease the staining of Tau-1, representing tau hyperphosphorylation at Ser262 (pS262) and Ser198/ 199/202 (Tau-1, as the antibody reacts with unphosphorylated tau, therefore, decreased staining represents increased phosphorylation). Pre-incubation of the brain slices with DHED could efficiently attenuate the CA-induced tau hyperphosphorylation at the above AD-related sites. Additionally, DHED also decreased the basal phosphorylation level of tau at Ser396, although CA failed to induce tau hyperphosphorylation at this site. Furthermore, CA treatment induced an increased level of Tyr307-phosphorylated PP-2A, which represents inactivation of the phosphatase, whereas DHED arrested the elevation of the inhibitory modification of PP-2A. Conclusion: DHED can attenuate CA-induced tau hyperphosphorylation at multiple AD-related sites in metabolically active rat brain slices. The underlying mechanism may involve a decreased inhibitory phosphorylation of PP-2A at Tyr307.

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Porous, Hollow, and Ball‐in‐Ball Metal Oxide Microspheres: Preparation, Endocytosis, and Cytotoxicity

et al. 2006

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Current technology relies heavily on composite materials, but in most cases, the size of the individual components have been micrometers or larger. The development of nanotechnology is driven in part by the desire to prepare materials that are only a few nanometers in size or that are made from components in the sub-micrometer regime. Improved preparations of various examples of monodisperse, [1] porous, [2] hollow, and/or core/shell [3] metal and semiconductor nanoparticles or nanowires [4] have been developed. We report here the use of a simple and scalable technology, ultrasonic spray pyrolysis (USP), [2e,5] to prepare porous, hollow, or ball-in-ball nanomaterials ( Fig. 1 and Supporting Information Fig. S1). In addition, we have investigated the cell toxicity (cytotoxicity) of these nanomaterials, in keeping with the growing concern of health effects that manmade nanoparticles could have now and in the near future.[6]Our interest in USP stems from our long standing work on the chemical and physical effects of ultrasound. [7a,b] In liquids irradiated with high-intensity ultrasound, acoustic cavitation produces high-energy chemistry through intense local heating inside the gas phase of collapsing bubbles in the liquid. [7] There are diverse applications of such sonochemistry, including the preparation of nanostructured materials and nanoparticles. USP presents an interesting inversion of the cavitation process.[2e,5j,k] Both confine the chemical reactions to isolated sub-micrometer reaction zones, but sonochemistry does so in a heated gas phase within a liquid, while USP uses a hot liquid droplet (or resulting heated solid particle) carried by a gas flow. Thus, we view USP as a method of phase-separated synthesis, in our cases, using sub-micrometer-sized droplets as isolated chemical reactors for nanomaterial synthesis. While USP has been used to create both titania and silica spheres separately, [2e,5b-d] there are no prior reports of titaniasilica composites. We have now produced such nanocomposites, and by further manipulation, generated various porous structures with fascinating morphologies (Figs. 1 and 2 and Supporting Information Fig. S3). As described in more detail in the Experimental section, a precursor solution was nebulized using a commercially available household ultrasonic humidifier (1.7 MHz ultrasound generator), and the resulting mist was carried in a gas stream through a glass tube in a hot furnace. After exiting the hot zone, spherical particles a few hundred nanometers in size (hereon referred to as microspheres) were collected in a water-filled bubbler as an aqueous colloidal solution. The microspheres were then isolated from this solution by centrifugation. Morphology, size distribution, and composition were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning TEM (STEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Cytotoxicity was tested with several whole mammalian cell assays.[8] Small molecules were also de...

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Pharmacokinetic Characterization of Dehydroevodiamine in the Rat Brain

Cited by 17 publications

References 17 publications

Functional Induction of P-glycoprotein in the Blood-Brain Barrier of Streptozotocin-Induced Diabetic Rats: Evidence for the Involvement of Nuclear Factor-κB, a Nitrosative Stress-Sensitive Transcription Factor, in the Regulation

Functional Induction of P-glycoprotein in the Blood-Brain Barrier of Streptozotocin-Induced Diabetic Rats: Evidence for the Involvement of Nuclear Factor-κB, a Nitrosative Stress-Sensitive Transcription Factor, in the Regulation

Dehydroevodiamine attenuates calyculin A-induced tau hyperphos-phorylation in rat brain slices

Porous, Hollow, and Ball‐in‐Ball Metal Oxide Microspheres: Preparation, Endocytosis, and Cytotoxicity

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