The Open Pharmacology Journal最新文献_第4页

Visualizing pharmacological activities of antidepressants: A novel approach 可视化抗抑郁药物的药理活性:一种新方法

The Open Pharmacology Journal Pub Date : 2008-06-03 DOI: 10.2174/1874143600802010054

H. J. Derijks, E. Heerdink, R. Janknegt, F. H. P. Koning, B. Olivier, A. Loonen, A. Egberts

引用次数: 26

Multiple Pathways of Apoptosis Induced by Roscovitine in Leukemic Cell Lines In Vitro 罗斯科维汀体外诱导白血病细胞凋亡的多种途径

The Open Pharmacology Journal Pub Date : 2008-04-11 DOI: 10.2174/1874143600802010024

Hairong Song, Å. Sidén, Z. Hassan

{"title":"Multiple Pathways of Apoptosis Induced by Roscovitine in Leukemic Cell Lines In Vitro","authors":"Hairong Song, Å. Sidén, Z. Hassan","doi":"10.2174/1874143600802010024","DOIUrl":"https://doi.org/10.2174/1874143600802010024","url":null,"abstract":"Roscovitine is a potent inhibitor of cyclin-dependent kinases (CDKs) that competes with the ATP binding pocket of kinases. Roscovitine has been shown to have cytotoxic effect on cancer cell lines in vitro and also in tumor xenografts in vivo. A strong synergistic effect in combination with conventional cytostatics has been reported in cancer cell lines in vitro. In this study, the mechanisms of roscovitineinduced cell death were investigated in human leukemic cell lines HL-60, Jurkat and K562. Cells were incubated with roscovitine (0.5-200 mol/L) up to 24 hours and cell viability and proliferation were studied using resazurin and H-thymidine incorporation assays, respectively. Cell cycle and mitochondrial membrane potential were analyzed using flow cytometry, apoptosis was assessed using morphological criteria in Giemsa staining and apoptotic pathways using Western blot analysis. Both viability and proliferation were inhibited in a concentration-dependent manner in all cell lines. Estimated IC50 was 17, 24 and 47 mol/L for HL-60, Jurkat and K562, respectively. Loss of mitochondrial membrane potential, release of cytochrome c, active fragment of caspase-3 and cleaved PARP were observed in all three cell lines. The cleaved fragments of caspase-2 and -8 were observed in HL-60 and Jurkat cells and the order of appearance differed between these two cell lines, while none of these fragments was observed in K562 cells. Thus, roscovitine is a potent inducer of apoptosis in leukemic cells and apoptosis has been mediated through different pathways depending on the cell line.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"14 1","pages":"24-30"},"PeriodicalIF":0.0,"publicationDate":"2008-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86518345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective Effect of 6-Gingerol Against Cardiotoxicity Induced by Doxorubicin 6-姜辣素对阿霉素所致心脏毒性的保护作用

The Open Pharmacology Journal Pub Date : 2008-03-27 DOI: 10.2174/1874143600802010020

M. Mansour, S. Bakheet, A. Aleisa, S. Al-Rejaie, A. Al-Yahya, Mubarak El-Ameen, O. Al‐shabanah

{"title":"Protective Effect of 6-Gingerol Against Cardiotoxicity Induced by Doxorubicin","authors":"M. Mansour, S. Bakheet, A. Aleisa, S. Al-Rejaie, A. Al-Yahya, Mubarak El-Ameen, O. Al‐shabanah","doi":"10.2174/1874143600802010020","DOIUrl":"https://doi.org/10.2174/1874143600802010020","url":null,"abstract":"Abstract: Doxorubicin (DOX) has a wide spectrum of antitumor activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from enhanced oxidative stress caused by oxygen centered free radicals. The present study was performed to investigate the influence of the antioxidant 6-gingerol on cardiotoxicity in-duced by doxorubicin (DOX). A single dose of DOX (20 mg/kg i.p.) induced myocardial toxicity after 48 hrs, manifested biochemically by a significant elevation in the following serum enzymes activities: creatine phosphokinase (E.C.2.7.3.2), lactate dehydrogenase (E.C.1.1.1.27), aspartate transaminase (E.C.2.6.1.1) and serum cardiac isoenzyme creatine phos-phokinase (MB). Administration of 6-gingerol (10 mg/kg/day p.o.) in drinking water starting 5 days before and continuing during the experimental period significantly ameliorated myocardial toxicity induced by DOX. The amelioration of car-diotoxicity was evidenced by significant reductions in serum enzymes activities and cardiac isoenzyme. The current data support 6-gingerol as a potentially selective cardioprotective agent, against cardiotoxicity induced by DOX and it may therefore improve the therapeutic index of DOX.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"55 1","pages":"20-23"},"PeriodicalIF":0.0,"publicationDate":"2008-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79465539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Effects of PKC and PKA Inhibitors on the cAMP-Stimulant-Induced Enhancement of Tetrodotoxin-Resistant Na + (Nav1.8) Currents PKC和PKA抑制剂对camp刺激诱导的抗河豚毒素Na + (Nav1.8)电流增强的影响

The Open Pharmacology Journal Pub Date : 2008-02-28 DOI: 10.2174/1874143600802010017

S. Matsumoto, S. Yoshida, M. Ikeda, C. Saiki, M. Takeda

引用次数: 2

Different Psychological States Sustain Drug-Induced Reactivation of Cocaine Conditioned Place Preference in the Mouse 不同心理状态维持药物诱导的可卡因条件位置偏好的再激活

The Open Pharmacology Journal Pub Date : 2008-02-14 DOI: 10.2174/1874143600802010001

T. Maurice, J. Espallergues, C. Zussy, J. Meunier, Clémence Borys, Elodie George, P. Romieu

{"title":"Different Psychological States Sustain Drug-Induced Reactivation of Cocaine Conditioned Place Preference in the Mouse","authors":"T. Maurice, J. Espallergues, C. Zussy, J. Meunier, Clémence Borys, Elodie George, P. Romieu","doi":"10.2174/1874143600802010001","DOIUrl":"https://doi.org/10.2174/1874143600802010001","url":null,"abstract":"Cocaine-seeking behavior can be investigated in rodents using the conditioned place preference (CPP) paradigm. CPP can be extinguished and then reactivated using cocaine priming. To study the role of dopaminergic receptors in CPP reinstatement, CPP was induced in Swiss mice using cocaine (30 mg/kg ip) and extinguished with saline. CPP reactivation was examined by treatment with the D1 receptor antagonist SCH23,390 (0.03-1 mg/kg), the D2 antagonist raclopride (0.1-3 mg/kg) or the D3 antagonist U-99,194A (20-40 mg/kg), alone or before cocaine (15 mg/kg). Cocaine priming reactivated CPP up to 220% of the post-conditioning response. SCH23,390 and raclopride induced, alone at 0.3 mg/kg, reactivation of cocaine-induced CPP, but only SCH23,390 blocked the cocaine-induced reactivation. U99,194A failed to promote CPP reactivation alone or to affect the cocaine response. CPP reactivation involving contextual learning could be induced using a single-reconditioning session after extinction. Treatment with cocaine or raclopride, but not SCH23,390, induced CPP reactivation. Finally, the emotional state of mice was tested during reactivation under drug treatments in the elevated maze procedure and an anxiety state was measured after 0.3 mg/kg SCH23,390. These observations showed that in cocaine-conditioned animals and then extinguished, blockade of D1 receptors induces an anxiogeniclike state, able to promote a cocaine-sensitive CPP reactivation. Blockade of D2 receptor promoted a cocaine-mimetic CPP reactivation. Therefore, two different psychological states underlie CPP reactivation by drug priming: a 'drug craving CPP' induced by dopamine systems-mediated anxiety and a 'drug retrieval CPP' promoted by incentive learning processes.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"52 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2008-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85230968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective Effect of Tegaserod Against Indomethacin-Induced Gastric Injury in the Rat 泰加塞罗德对吲哚美辛致大鼠胃损伤的保护作用

The Open Pharmacology Journal Pub Date : 2008-02-12 DOI: 10.2174/1874143600802010010

K. Venkova, D. Earnest, B. Meerveld

引用次数: 6

Cyclophosphamide Pharmacokinetics in Mice: A Comparison Between Retro Orbital Sampling Versus Serial Tail Vein Bleeding 环磷酰胺在小鼠体内的药代动力学:复古眼眶取样与连续尾静脉出血的比较

The Open Pharmacology Journal Pub Date : 2008-01-07 DOI: 10.2174/1874143600701010030

R. Said, M. Abdel-Rehim, B. Sadeghi, S. Al-Hashemi, Z. Hassan, Moustapha Hassan

{"title":"Cyclophosphamide Pharmacokinetics in Mice: A Comparison Between Retro Orbital Sampling Versus Serial Tail Vein Bleeding","authors":"R. Said, M. Abdel-Rehim, B. Sadeghi, S. Al-Hashemi, Z. Hassan, Moustapha Hassan","doi":"10.2174/1874143600701010030","DOIUrl":"https://doi.org/10.2174/1874143600701010030","url":null,"abstract":"Preclinical studies on pharmacokinetics in animals usually require at least 3-5 animals per time point. The use of several animals in each time point may increase the result variation due to individual dosing errors and interand intraindividual variation among animals. Moreover, a large number of animals has to be euthanized in these experiments. In the present paper, the pharmacokinetics of the anticancer drug, cyclophosphamide was investigated using serial bleeding from the tail vein and compared with the kinetics obtained from traditional retro-orbital sinus bleeding in mice. Cyclophosphamide (100 mg/kg) was administered intraperitoneally to two groups of mice. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 and 6 hr. In the first group (n=6), 20 L blood samples were collected from the tail-vein by serial bleeding. In the second group, 3 animals were killed at each time point and blood was collected from both tail vein and retro-orbital sinus. Cyclophosphamide analysis in whole blood was carried out using LC-MS/MS with on-line sample preparation utilizing microextraction by packed sorbent (MEPS). Pharmacokinetics including AUC, tmax, Cmax and half – life were estimated using WinNonLin. Cyclophosphamide concentrations in blood obtained after sampling through tail vein were close to those obtained after retro-orbital bleeding within the same animal. No significant differences in estimated pharmacokinetic parameters were found when serial tail vein bleeding was compared to retro-orbital bleeding. Our results indicate that serial sampling using tail vein in mice can be a good alternative to retro-orbital sampling method. The method is reliable, easy and can be used for early preclinical kinetic studies. However, more studies are needed to evaluate different drug categories.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"39 1","pages":"30-35"},"PeriodicalIF":0.0,"publicationDate":"2008-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88683865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

Mechanisms of acute cocaine toxicity. 可卡因急性毒性的机理。

The Open Pharmacology Journal Pub Date : 2008-01-01 DOI: 10.2174/1874143600802010070

Kennon Heard, Robert Palmer, Nancy R Zahniser

引用次数: 0

Potential Benefits of Peroxynitrite. 过氧化亚硝酸盐的潜在益处。

The Open Pharmacology Journal Pub Date : 2008-01-01 DOI: 10.2174/1874143600802010031

Bobby D Nossaman, Philip J Kadowitz

引用次数: 0

HCV and Diabetes Mellitus: Considerations About Effects of Interferon Therapy 丙型肝炎与糖尿病:干扰素治疗效果的考虑

The Open Pharmacology Journal Pub Date : 2007-12-13 DOI: 10.2174/1874143600701010027

L. Reynaud, M. A. Carleo, M. Talamo, G. Borgia

引用次数: 0