当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Mdr1a plays a crucial role in regulating the analgesic effect and toxicity of aconitine by altering its pharmacokinetic characteristics.

Mdr1a plays a crucial role in regulating the analgesic effect and toxicity of aconitine by altering its pharmacokinetic characteristics.

Abstract：

:Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a-/- FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a-/- mice (49% to 105%) compared to wild-type mice (P<0.05). The levels of s100-β protein and creatine kinase, which indicate cerebral and myocardial damage, respectively, were also significantly increased (P<0.05) in Mdr1a-/- mice. Histopathological examination revealed that the Mdr1a-/- mice suffered from evident cerebral and myocardial damages, but the wild-type mice did not. These findings suggested that Mdr1a deficiency significantly promoted the analgesic effect of AC and exacerbated its toxicity. Pharmacokinetic experiments showed that T1/2 of AC in the Mdr1a-/- mice was significantly higher (from 87% to 300%) than that in wild-type mice (P<0.05). The distribution of AC in the brain of Mdr1a-/- mice was 2- to 32-fold higher than that in the brains of wild-type mice (P<0.05). Toxic reactions were more severe in Mdr1a-/- mice compared to wild-type mice. In conclusion, Mdr1a deficiency significantly enhanced the analgesic effect of AC and exacerbated its toxicity by upregulating its distribution to the brain and decreasing its plasma elimination rate. Thus, Mdr1a dysfunction may cause severe AC poisoning.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Zhu L,Wu J,Zhao M,Song W,Qi X,Wang Y,Lu L,Liu Z

doi

10.1016/j.taap.2017.02.008

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

32-39

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(17)30065-0

journal_volume

320

pub_type

杂志文章

相关文献

TOXICOLOGY AND APPLIED PHARMACOLOGY文献大全
  • Anabolic-androgenic steroid-induced toxicity in primary neonatal rat myocardial cell cultures.

    abstract：:Recent literature reports of myocardial infarction in athletes who self-administer anabolic-androgenic steroid (AAS) and previous animal studies of the effects of AASs on the heart suggest that these drugs may be directly injurious to the myocardium. We have previously demonstrated that 100 microM testosterone cypiona...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1995.1158

    authors： Welder AA,Robertson JW,Fugate RD,Melchert RB

    更新日期：1995-08-01 00:00:00

  • Acetaminophen-induced cytotoxicity in cultured mouse hepatocytes: correlation of nuclear Ca2+ accumulation and early DNA fragmentation with cell death.

    abstract：:Hepatotoxic doses of acetaminophen cause widespread alkylation of liver and early loss of cytosolic Ca2+ regulation. Although the precise location and target of lethal alkylation are not known, Ca2+ accumulation is viewed as a possible link between cell alkylation and cell death. We have recently shown that Ca2+ accum...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(91)90028-d

    authors： Shen W,Kamendulis LM,Ray SD,Corcoran GB

    更新日期：1991-11-01 00:00:00

  • Microarray analysis of changes in bone cell gene expression early after cadmium gavage in mice.

    abstract：:We developed an in vivo model for cadmium-induced bone loss in which mice excrete bone mineral in feces beginning 8 h after cadmium gavage. Female mice of three strains [CF1, MTN (metallothionein-wild-type), and MT1,2KO (MT1,2-deficient)] were placed on a low-calcium diet for 2 weeks. Each mouse was gavaged with 200 m...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0041-008x(03)00163-7

    authors： Regunathan A,Glesne DA,Wilson AK,Song J,Nicolae D,Flores T,Bhattacharyya MH

    更新日期：2003-09-15 00:00:00

  • Lactate dehydrogenase isoenzymes in hamster lung lavage fluid after lung injury.

    abstract：:Lactate Dehydrogenase Isoenzymes in Hamster Lung Lavage Fluid after Lung Injury. Beck, B. D., Gerson, B., Feldman, H. A., and Brain, J. D. (1983). Toxicol. Appl. Pharmacol. 71, 59-71. Lactate dehydrogenase (LD) levels and isoenzyme patterns were determined in the cell-free supernatant fractions of lung lavage fluid fr...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(83)90045-5

    authors： Beck BD,Gerson B,Feldman HA,Brain JD

    更新日期：1983-10-01 00:00:00

  • Microarray analysis of altered gene expression in murine fibroblasts transformed by nickel(II) to nickel(II)-resistant malignant phenotype.

    abstract：:B200 cells are Ni(II)-transformed mouse BALB/c-3T3 fibroblasts displaying a malignant phenotype and increased resistance to Ni(II) toxicity. In an attempt to find genes whose expression has been altered by the transformation, the Atlas Mouse Stress/Toxicology cDNA Expression Array (Clontech Laboratories, Inc., Palo Al...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2004.10.006

    authors： Kowara R,Karaczyn A,Cheng RY,Salnikow K,Kasprzak KS

    更新日期：2005-05-15 00:00:00

  • Effects of benzo[a]pyrene on concanavalin A-stimulated human peripheral blood mononuclear cells in vitro: inhibition of proliferation but no effect on parameters related to the G1 phase of the cell cycle.

    abstract：:The immunotoxic effects of the environmental carcinogen benzo[a]pyrene (BaP) have been evaluated using mouse, but not human, lymphocytes. Since susceptibility to immunomodulation by BaP may be species-related, the effects of BaP on human peripheral blood mononuclear cells (HPBMC) from several individuals were investig...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1993.1057

    authors： Mudzinski SP

    更新日期：1993-04-01 00:00:00

  • Influence of the Ah locus on the humoral immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: evidence for Ah-receptor-dependent and Ah-receptor-independent mechanisms of immunosuppression.

    abstract：:There are conflicting reports in the literature regarding the role of the Ah locus in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity. The present studies have utilized two congenic strains of C57Bl/6 mice that differ only at this locus to assess its influence on TCDD-induced suppression of antibody response...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(90)90356-y

    authors： Kerkvliet NI,Steppan LB,Brauner JA,Deyo JA,Henderson MC,Tomar RS,Buhler DR

    更新日期：1990-08-01 00:00:00

  • Disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran by rainbow trout (Oncorhynchus mykiss).

    abstract：:The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1996.0183

    authors： Steward AR,Maslanka R,Pangrekar J,Kumar S,Sikka HC

    更新日期：1996-08-01 00:00:00

  • Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.

    abstract：:The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2017.07.019

    authors： Brillant N,Elmasry M,Burton NC,Rodriguez JM,Sharkey JW,Fenwick S,Poptani H,Kitteringham NR,Goldring CE,Kipar A,Park BK,Antoine DJ

    更新日期：2017-10-01 00:00:00

  • Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2.

    abstract：BACKGROUND:The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2021.115425

    authors： Kalarikkal SP,Sundaram GM

    更新日期：2021-01-28 00:00:00

  • Comparative analysis of lung and blood transcriptomes in mice exposed to multi-walled carbon nanotubes.

    abstract：:Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) causes inflammation, fibroproliferation, immunotoxicity, and systemic responses in rodents. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identif...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2020.114898

    authors： Khaliullin TO,Yanamala N,Newman MS,Kisin ER,Fatkhutdinova LM,Shvedova AA

    更新日期：2020-03-01 00:00:00

  • Cytotoxicity and induction of proinflammatory cytokines from human monocytes exposed to fine (PM2.5) and coarse particles (PM10-2.5) in outdoor and indoor air.

    abstract：:Increased incidence of mortality and morbidity due to cardiopulmonary complications has been found to associate with elevated levels of particulate air pollution (particulate matter with an aerodynamic diameter < 10 microm, PM10 and <2.5 microm, PM2. 5). Lung injury and an imbalance of inflammatory mediators are propo...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1998.8591

    authors： Monn C,Becker S

    更新日期：1999-03-15 00:00:00

  • Chemically induced growth inhibition and cell cycle perturbations in cultures of differentiating rodent embryonic cells.

    abstract：:Ethylnitrosourea (ENU) is a proven animal teratogen, although the mechanism of its developmental toxicity is unknown. The micromass rat embryo midbrain (CNS) and limb bud (LB) cultures were used in an effort to determine potential mechanisms by which ENU may exert its teratogenic effect. When cultured at high cell den...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(90)90295-6

    authors： Ribeiro PL,Faustman EM

    更新日期：1990-06-15 00:00:00

  • Heme oxygenase-1 attenuates low-dose of deoxynivalenol-induced liver inflammation potentially associating with microbiota.

    abstract：:Deoxynivalenol (DON) is one of the most common mycotoxins which contaminate cereals and their by-products worldwide. Previous studies have stated toxic effects of DON on liver. Heme oxygenase-1 (HO-1) plays a potential role in protecting liver and maintaining gut microbiota homeostasis. Therefore, a study on the poten...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2019.04.020

    authors： Peng Z,Liao Y,Chen L,Liu S,Shan Z,Nüssler AK,Yao P,Yan H,Liu L,Yang W

    更新日期：2019-07-01 00:00:00

  • Comparative lung tumorigenicity of parent and mononitro-polynuclear aromatic hydrocarbons in the BLU:Ha newborn mouse assay.

    abstract：:A BLU:Ha newborn mouse lung adenoma bioassay was employed to compare the tumorigenicity of selected mononitroarenes and unsubstituted parent compounds 6 months after initial treatment. The presence of a nitro group had a variable effect upon compound potency in which tumorigenicity was increased, abolished, or unchang...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(89)90162-2

    authors： Busby WF Jr,Stevens EK,Martin CN,Chow FL,Garner RC

    更新日期：1989-07-01 00:00:00

  • Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat.

    abstract：:This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were comp...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2012.03.005

    authors： Al-Subeihi AA,Spenkelink B,Punt A,Boersma MG,van Bladeren PJ,Rietjens IM

    更新日期：2012-05-01 00:00:00

  • Activation of the activator protein-1 by the peroxisome proliferator clofibric acid in rat H4IIEC3 hepatoma cells.

    abstract：:Clofibric acid (CA), a potent peroxisome proliferator (PP), has been shown to cause tumor formation in rat liver. The precise mechanism of action of PPs remains largely unknown. However, it has been proposed that they act by increasing reactive oxygen species (ROS), leading to a cellular oxidative stress. In the prese...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.2001.9214

    authors： Bécuwe P,Bianchi A,Dauça M

    更新日期：2001-08-01 00:00:00

  • Effects of adsorption of benzo[a]pyrene onto carbon black particles on levels of DNA adducts in lungs of rats exposed by inhalation.

    abstract：:Exposure of rodents to benzo[a]pyrene (BaP) associated with particles has previously been shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA damage might be enhanced, DNA adducts were measured in lungs of F344 rats following inhalation of pure BaP aerosols or BaP absorbed on ca...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(89)90334-7

    authors： Wolff RK,Bond JA,Sun JD,Henderson RF,Harkema JR,Griffith WC,Mauderly JL,McClellan RO

    更新日期：1989-02-01 00:00:00

  • 4-Hydroxy-2-nonenal enhances fibronectin production by IMR-90 human lung fibroblasts partly via activation of epidermal growth factor receptor-linked extracellular signal-regulated kinase p44/42 pathway.

    abstract：:To elucidate the underlying mechanisms in oxidative stress-related airway remodeling observed in chronic inflammatory pulmonary diseases such as asthma, we studied the effects of a thiol antioxidant, N-acetylcysteine (NAC), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AG-1478, and tyr...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.2002.9514

    authors： Tsukagoshi H,Kawata T,Shimizu Y,Ishizuka T,Dobashi K,Mori M

    更新日期：2002-11-01 00:00:00

  • Characterization of deltamethrin metabolism by rat plasma and liver microsomes.

    abstract：:Deltamethrin, a widely used type II pyrethroid insecticide, is a relatively potent neurotoxicant. While the toxicity has been extensively examined, toxicokinetic studies of deltamethrin and most other pyrethroids are very limited. The aims of this study were to identify, characterize, and assess the relative contribut...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2005.07.021

    authors： Anand SS,Bruckner JV,Haines WT,Muralidhara S,Fisher JW,Padilla S

    更新日期：2006-04-15 00:00:00

  • Distinct MAPK signaling pathways, p21 up-regulation and caspase-mediated p21 cleavage establishes the fate of U937 cells exposed to 3-hydrogenkwadaphnin: differentiation versus apoptosis.

    abstract：:Despite the depth of knowledge concerning the pathogenesis of acute myeloblastic leukemia (AML), long-term survival remains unresolved. Therefore, new agents that act more selectively and more potently are required. In that line, we have recently characterized a novel diterpene ester, called 3-hydrogenkwadaphnin (3-HK...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2008.02.010

    authors： Moosavi MA,Yazdanparast R

    更新日期：2008-07-01 00:00:00

  • Late dimethyl sulfoxide administration provides a protective action against chemically induced injury in both the liver and the kidney.

    abstract：:Dimethyl sulfoxide (DMSO) can protect the liver from injury produced by a variety of hepatotoxicants when administered prior to or concomitant with the toxicants. This protective action has previously been attributed to DMSO-induced inhibition of bioactivation of the compounds to toxic intermediates. In these studies,...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1996.8009

    authors： Lind RC,Gandolfi AJ

    更新日期：1997-01-01 00:00:00

  • Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase.

    abstract：:Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-ass...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2005.12.008

    authors： Li B,Duysen EG,Poluektova LY,Murrin LC,Lockridge O

    更新日期：2006-07-15 00:00:00

  • Plasma membrane-specific phospholipase A1 activation by nitrogen dioxide in pulmonary artery endothelial cells.

    abstract：:Nitrogen dioxide (NO2), an environmental oxidant, alters the plasma membrane structure and function of pulmonary artery endothelial cells through peroxidative injury. Because perioxidative injury can activate membrane phospholipases and alter phospholipid composition of membranes, we evaluated the effects of NO2 expos...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(91)90317-8

    authors： Sekharam KM,Patel JM,Block ER

    更新日期：1991-03-01 00:00:00

  • Polychlorinated biphenyl-induced apoptosis of murine spleen cells is aryl hydrocarbon receptor independent but caspases dependent.

    abstract：:Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and many of their toxic effects, including their immunotoxicities, are mediated by the activation of aryl hydrocarbon receptor (AhR). We previously reported that Aroclor 1254, one of the most widely used PCB mixtures, increased DNA fragmentatio...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.2002.9389

    authors： Jeon YJ,Youk ES,Lee SH,Suh J,Na YJ,Kim HM

    更新日期：2002-06-01 00:00:00

  • Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line.

    abstract：:Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and pre...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2016.03.009

    authors： Vendramini-Costa DB,Alcaide A,Pelizzaro-Rocha KJ,Talero E,Ávila-Román J,Garcia-Mauriño S,Pilli RA,de Carvalho JE,Motilva V

    更新日期：2016-06-01 00:00:00

  • Fumonisin B1 induces protein kinase C translocation via direct interaction with diacylglycerol binding site.

    abstract：:Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1996.0274

    authors： Yeung JM,Wang HY,Prelusky DB

    更新日期：1996-11-01 00:00:00

  • Atorvastatin and insulin equally mitigate brain pathology in diabetic rats.

    abstract：:Although insulin and atorvastatin have been shown to exert glycemic control and could improve brain function, the effects of atorvastatin or insulin as well as the combination of atorvastatin plus insulin on brain pathology in diabetes mellitus type 1 (T1DM) are unclear. Therefore, this study investigated the effect o...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2018.01.021

    authors： Pratchayasakul W,Thongnak LO,Chattipakorn K,Lungaphin A,Pongchaidecha A,Satjaritanun P,Jaiwongkam T,Kerdphoo S,Chattipakorn SC

    更新日期：2018-03-01 00:00:00

  • Regulation of phenobarbital-inducible cytochrome P450 2B1/2 mRNA by lovastatin and oxysterols in primary cultures of adult rat hepatocytes.

    abstract：:Lovastatin (LOVA) is a potent inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase widely used in clinical practice. We treated primary cultures of adult rat hepatocytes, maintained in a minimal, serum-free medium on Matrigel, a reconstituted basement membrane, with this drug, and found that the amounts of P450...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1993.1115

    authors： Kocarek TA,Schuetz EG,Guzelian PS

    更新日期：1993-06-01 00:00:00

  • Mercury (Hg 2+) enhances the depressant effect of kainate on Ca-inactivated potassium current in telencephalic cells derived from chick embryos.

    abstract：:The effect of HgCl2 on kainate (KA)-induced depression of voltage-gated potassium (K+) current in chick embryo telencephalic cells was studied using conventional and nystatin-perforated whole-cell patch-clamp recordings, fluorescence imaging, and flow cytometry techniques. Hg2+ (1 microM) alone did not effect the 4-am...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1996.0127

    authors： Dyatlov VA,Platoshin AV,Lawrence DA,Carpenter DO

    更新日期：1996-06-01 00:00:00