Abstract:
:Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX-SIM-Solution) or nanoemulsions (NEs) (DOX-SIM-NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX-SIM-Solution group (265.30) that was double the %ILS of the DOX-SIM-NE group (134.70). However, DOX-SIM-NE had a non-toxic effect on the haematological parameters, whereas DOX-SIM-Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX-SIM-Solution. A reduction in the side effects of DOX-SIM-NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX-SIM-NE treatment than with the DOX-SIM-Solution treatment. The study showed that incorporating SIM into the DOX-loaded-NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Alkreathy HM,Alkhatib MH,Al Musaddi SA,Balamash KSA,Osman NN,Ahmad Adoi
10.1111/1440-1681.13071subject
Has Abstractpub_date
2019-05-01 00:00:00pages
496-505issue
5eissn
0305-1870issn
1440-1681journal_volume
46pub_type
杂志文章abstract::In guinea-pig isolated atria, angiotensin I and angiotensin II produced concentration dependent increases in the rate of spontaneous beating and in the release of noradrenaline produced by field stimulation of sympathetic nerves. In rat isolated caudal artery preparations, both angiotensin I and angiotensin II had dir...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00290.x
更新日期:1984-07-01 00:00:00
abstract::To test a possible role of endogenous opioids in the blood pressure (BP) and heart rate (HR) responses to the converting enzyme inhibitor captopril in man, nine normal subjects were given captopril (50 mg) or placebo with and without the opioid antagonist naloxone (0.2 mg/kg i.v.). Treatments were given in random orde...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1983.tb00192.x
更新日期:1983-05-01 00:00:00
abstract::1. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03202.x
更新日期:2000-01-01 00:00:00
abstract::This study evaluates the association between the long noncoding RNA GAS5 levels and the anti-proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP pl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12572
更新日期:2016-06-01 00:00:00
abstract::Osteosarcoma is the most common non-hematological primary bony malignancy in children and young adults with tumor metastasis being a common event at diagnosis. Understanding the pathogenesis of metastatic osteosarcoma may help identify potential therapeutic targets. In this study, we found that the level of microRNA-6...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13006
更新日期:2018-12-01 00:00:00
abstract::Severe drug eruption (SDE), a common skin disease, becomes dangerous when it occurs in patients with human immunodeficiency virus (HIV). However, the molecular mechanisms are poorly understood. Forty patients including HIV+ SDE+ (n = 15), HIV- SDE+ (n = 15) and HIV+ SDE- (n = 10) subjects were enrolled in our study. A...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13266
更新日期:2020-06-01 00:00:00
abstract::1. The intrinsic sympathomimetic activity of a range of beta-adrenoceptor antagonists and its relationship to beta-adrenoceptor blockade was studied in pentobarbitone-anaesthetized, vagotomized rats which had been depleted of catecholamines by pretreatment with syrosingopine. Dichlorisoprenaline, practolol, oxprenolol...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00001.x
更新日期:1979-01-01 00:00:00
abstract::1. Ionic channels appear to play an important role in contractile responses of the cerebral arteries and, thereby, contribute to the regulation of cerebral circulation. In the present study, we investigated the role of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in the regulation of cerebral arterial tone ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03688.x
更新日期:2002-07-01 00:00:00
abstract::1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03913.x
更新日期:2003-10-01 00:00:00
abstract::1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05213.x
更新日期:2009-12-01 00:00:00
abstract::1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types. 2. As with all other active analogues of CPT, irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb01158.x
更新日期:1996-10-01 00:00:00
abstract::1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway pr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03483.x
更新日期:2001-07-01 00:00:00
abstract::1. The leucocyte-mediated inflammatory response plays a pivotal role in ischaemia-reperfusion injury. P-Selectin and CD11b are important mediators for the recruitment of leucocytes into the endothelium. However, the time-course of changes in P-selectin and CD11b expression during reperfusion is not defined. Magnesium ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04697.x
更新日期:2007-12-01 00:00:00
abstract::1. Oxidative stress plays a role in senescence-associated organ deterioration. This is supported by the beneficial effects of anti-oxidants against ageing-related organ damage, although their role in cardiac ageing has not been elucidated. 2. The aim of the present study was to examine the impact of cardiac-specific o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04540.x
更新日期:2007-01-01 00:00:00
abstract::1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 +/- 3.9 v...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04102.x
更新日期:2004-12-01 00:00:00
abstract::1. Electrolytic lesions were made in various brain regions of the rat, and the effects of these lesions on nociceptive threshold and the antinociceptive actions of morphine were tested using a shock titration technique. 2. Lesions in the medial thalamus, the periaqueductal grey area, or the caudate nucleus, had no eff...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb03031.x
更新日期:1975-05-01 00:00:00
abstract::1. A method is described which allows the determination of liquid junction potentials between biological fluid samples of less than 1 nL with a reproducibility of 10%. This was achieved by use of a micro-method and the use of 3% agarose added to the electrolyte in the measuring electrodes. 2. Validation was performed ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01605.x
更新日期:1989-07-01 00:00:00
abstract::1. The influence of the passive force on the contraction and endothelium-dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. 2. Force changes of endothelium-intact and -removed preparations were measured isometrically by a force...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02765.x
更新日期:1996-06-01 00:00:00
abstract::1. Activities of acetylcholinesterase (AChE), neuropathy target esterase (NTE), and carboxylesterase (CbxE) were compared in neuroblastoma cells of human origin (SH-SY5Y) and murine origin (NB41A3). 2. Mouse neuroblastoma cells had lower specific activities of NTE and CbxE than did human neuroblastoma cells; specific ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb02027.x
更新日期:1995-05-01 00:00:00
abstract::1. Resveratrol (RSV), a polyphenol in red wine, exhibits cardioprotective effects in vitro, such as inhibition of angiotensin II- or phenylephrine-induced cardiomyocyte hypertrophy in rat neonatal myocyte cultures and suppression of cardiac fibroblast proliferation. The aim of the present study was to investigate the ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05231.x
更新日期:2010-02-01 00:00:00
abstract::1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03552.x
更新日期:2001-11-01 00:00:00
abstract::The anti-acetylcholinesterase (AChEase) activity of 15 opioids, namely morphine, nalorphine, oxymorphone, naloxone, naltrexone, N-methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo-methadone, dextro-methadone, pethidine, leu-enkephalin and U-50,488H was investigated. Among the opioids, the morp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00330.x
更新日期:1986-02-01 00:00:00
abstract::1. Mathematical modelling is useful in pharmacology, allowing the investigator to obtain insights into the biological processes under study that may not always be intuitively obvious. Examples are presented in this review using the pharmacology of the muscarinic acetylcholine receptor (mAChR) agonist xanomeline. 2. Xa...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03376.x
更新日期:2001-03-01 00:00:00
abstract::1. The therapeutic effect of green tea extract (GTE) on the aortic collagen content and its characteristics were investigated in streptozotocin diabetic rats. 2. Diabetes was induced in rats by a single intra peritoneal injection of streptozotocin (60 mg/kg bodyweight). Six weeks after diabetes induction, GTE was admi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04374.x
更新日期:2006-04-01 00:00:00
abstract::1. The present study was designed to determine the effects of ginkgolide A, ginkgolide B and quercetin on CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes. 2. Hepatocytes were pretreated with ginkgolide A, ginkgolide B and quercetin (at 1, 3, 10 and 30 micromol/L) for 48 h and then...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04630.x
更新日期:2007-07-01 00:00:00
abstract::1. Two patients with angiotensin-responsive aldosterone-producing adenoma (APA) and one with adrenal cortical carcinoma demonstrated autonomous secretion of cortisol as well as of aldosterone. 2. The response of cortisol and of aldosterone to ACTH did not differentiate between the two APA which secreted cortisol and t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01300.x
更新日期:1990-03-01 00:00:00
abstract::1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]-inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose-dependent increases in the accumulation of inositol mono, bis and trisphosphates ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01320.x
更新日期:1990-04-01 00:00:00
abstract::1. The effects of 14 lignocaine homologues on the maximum upstroke velocity (Vmax) of the action potentials (AP) were studied in guinea-pig papillary muscles. These drugs possess one, two or three methyl groups in different positions: an ortho-chloro, -carbomethoxy or -ethyl group instead of an ortho-methyl group; or ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00489.x
更新日期:1992-06-01 00:00:00
abstract::1. Activation of peripheral chemoreceptors with KCN in the working heart-brainstem preparation from young male Wistar rats (70-90 g) increases phrenic (PNA; +105 +/- 18%) and thoracic (tSNA; +44 +/- 6%) sympathetic nerve activity compared with baseline and reduces heart rate (HR; from 377 +/- 27 to 83 +/- 6 b.p.m.). 2...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2005.04213.x
更新日期:2005-05-01 00:00:00
abstract::1. In the mammalian central nervous system, GABA is the main inhibitory neurotransmitter. GABA is a highly flexible molecule and, thus, can exist in many low-energy conformations. Conformationally restricted analogues of GABA have been used to help identify three major GABA receptors, termed GABAA, GABAB and GABAC rec...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03151.x
更新日期:1999-11-01 00:00:00