Abstract:
:Lipid peroxidation is a major consequence of oxidative stress and an important cause of neuronal damage in ischaemic injuries and neurodegenerative disorders such as Parkinson's disease. Recent research has focused on the development of antioxidant drugs which may delay or minimize neurodegeneration. Rapid and reliable assays are therefore necessary in order to evaluate novel antioxidant compounds. A widely adopted method for measurement of lipid peroxidation is the thiobarbituric acid reacting substances (TBARS) assay. Several variations of this method have appeared in the literature, some of which have been tested by us without success. We have therefore established a reliable procedure which takes into account the most important factors previously found to influence the TBARS method. Briefly, various concentrations of drug were added to rat brain homogenates (10% w/v in 20 mM Tris-HCl buffer, pH 7.4) and incubated at 37 degrees C for 10 min before addition of ammonium ferric sulphate (100 or 1000 microM) and a further incubation at 37 degrees C for 30 min. Proteins were then precipitated with 8.1% sodium dodecyl sulphate, the reaction stopped with 20% acetic acid, and the samples were then centrifuged for 15 min. Aliquots of supernatant were added to an equal volume of thiobarbituric acid (0.8%), samples were heated at 95 degrees C for 30 min, and then cooled on ice before reading at 532 nm. The present adaptation represents a simple and highly reproducible assay which does not require difficult extraction procedures with hazardous chemicals and results in a stable chromagen. The method has been evaluated using a number of structurally distinct antioxidants and iron chelators. IC50 values (microM) for percentage inhibition of TBARS formation were as follows: desferroxamine (1.1), U83836E (1.7), butylated hydroxytoluene (13), U74500A (20), LY231617 (22), idebenone (89), and Trolox (110). This order of potency was comparable to that found with a commercially available, but expensive kit designed to specifically measure malondialdehyde (Spearman's rank correlation coefficient, p < 0.01).
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Callaway JK,Beart PM,Jarrott Bdoi
10.1016/s1056-8719(98)00022-7subject
Has Abstractpub_date
1998-04-01 00:00:00pages
155-62issue
3eissn
1056-8719issn
1873-488Xpii
S1056-8719(98)00022-7journal_volume
39pub_type
杂志文章abstract:INTRODUCTION:The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. METHODS:Laplace transforms...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.03.004
更新日期:2015-05-01 00:00:00
abstract::Toxicogenomics, the application of genomic data to elucidate or predict an organism's response to a toxicant, can inform the drug development process in important ways. It is apparent that standardized approaches to many types of toxicogenomic questions are still being formulated. Specifically, a significant body of p...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/j.vascn.2005.05.006
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Different methods for the analysis of behavioral observation data were compared to evaluate how the interpretation of a data set may depend on the analysis method employed. METHODS:Three methods of analysis were used to evaluate the same four sets of rodent behavioral FOB data: (1) evaluation by a trained...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2010.06.001
更新日期:2010-09-01 00:00:00
abstract::For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variati...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(94)90060-4
更新日期:1994-10-01 00:00:00
abstract:INTRODUCTION:Simultaneous recording of electrical potentials from multiple cells may be useful for physiological and pharmacological research. The present study aimed to establish an in vitro cardiac hypoxia experimental platform on the microelectrode array (MEA). METHODS:Embryonic rat cardiac myocytes were cultured o...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.02.005
更新日期:2009-05-01 00:00:00
abstract:INTRODUCTION:The ability to quantify systemic concentrations of protein therapeutics is complicated by the presence of endogenous analyte, specific binding proteins, and nonspecific matrix components in biological matrices (Lee & Ma, 2007). Further complications can be introduced following pegylation whereby polyethyle...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.12.004
更新日期:2010-03-01 00:00:00
abstract::A model of gingival inflammation was performed in Sprague-Dawley rats weighing 180-200 g. Mechanical bamboo stick-induced injury was inflammatory when bacteria contaminated the sticks. Bacteria were first obtained from gingival fluid collected from a patient with adult periodontitis. Another strain from Institut Paste...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(94)90070-1
更新日期:1994-11-01 00:00:00
abstract::We report a simple fluorometric method for the continuous monitoring of mitochondrial membrane potential and cell viability in suspensions of hepatocytes exposed in vitro to cytotoxic agents. Suspensions of freshly isolated hepatocytes (10(6) cells/mL) preloaded with rhodamine 123 (Rh 123, 100 mumol/L) are transferred...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(95)00131-x
更新日期:1996-02-01 00:00:00
abstract:INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.06.002
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:A Tecan-based enzyme inhibition assay has been developed for the determination of atorvastatin-derived 'active' and 'total' (active inhibitors plus atorvastatin lactone and other potential inhibitors following base hydrolysis) 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor concentratio...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.06.002
更新日期:2008-01-01 00:00:00
abstract::The potentiation of the antinociceptive effect of morphine by dipyrone (metamizol) and the possible participation of a peripheral mechanism on such synergism were studied with the use of the formalin test in the rat. Nociception was induced by the intraplantar injection of diluted formalin (1%) in the right hind paw. ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(00)00046-0
更新日期:1999-10-01 00:00:00
abstract::The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving trai...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2011.07.002
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:The combined evaluation of physiology and behaviour allows a complete and more comprehensive pre-clinical assessment of central nervous system (CNS) function. An integrated video-telemetric electroencephalography (Video-tEEG) system, which allows the simultaneous and continuous recording of EEG and video i...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2010.04.004
更新日期:2010-07-01 00:00:00
abstract:INTRODUCTION:There has been an increasing need to conduct investigative safety pharmacology studies to complement regulatory-required studies, particularly as it applies to a comprehensive assessment of cardiovascular (CV) risk. METHODS:We describe refined methodology using a combination of telemetry and direct signal...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2016.05.002
更新日期:2016-09-01 00:00:00
abstract::Guinea pigs were sensitized with ovalbumin (i.p.) 14 days before use. In vivo airway hyperreactivity induced by ovalbumin inhalation was determined by challenging with aerosolized spasmogen (5-hydroxytryptamine [5-HT] methacholine, the thromboxane-mimetic, U-46619, or adenosine) 24 hr before (7 days with adenosine) an...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(95)00093-3
更新日期:1995-12-01 00:00:00
abstract::Electrical field stimulation (EFS, 2.5 Hz, 60 V, 1 ms, trains of 5 sec every 5 min) of the rat external urethral sphincter (EUS) produced contractile responses characterized by a "slow" tonic contraction on which was superimposed a series of phasic "twitch-like" contractions. Both responses were abolished by tetrodoto...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(92)90052-3
更新日期:1992-09-01 00:00:00
abstract::The U.S. Food & Drug Administration (FDA) has issued a final guidance document on the preclinical determination of abuse potential that must be conducted in animals for all new molecular entities (NMEs) submitted for a new drug application (NDA). Under statutory restrictions government guidance documents serve only as...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2017.11.005
更新日期:2018-01-01 00:00:00
abstract:INTRODUCTION:The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats propo...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2012.09.002
更新日期:2013-03-01 00:00:00
abstract::In this study a new model of cerebral ischemia, based on a middle cerebral artery (MCA) thrombosis in rats is described. Furthermore, the effect of the novel plasminogen activator (SUN9216), a plasminogen-plasminogen activator chimera, comprising the fibrin kringle 1 domain of a plasminogen, and the two kringles, and ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(93)90068-p
更新日期:1993-06-01 00:00:00
abstract:INTRODUCTION:We characterised the development of Type 2 diabetes and associated changes in islet appearance in female ZDF rats and explored its suitability for studies with novel therapeutic agents. METHODS:Female ZDF rats were either chow or high fat (60%) fed for up to 36 days and blood glucose and plasma insulin co...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2010.04.001
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT p...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,多中心研究
doi:10.1016/j.vascn.2015.12.002
更新日期:2016-03-01 00:00:00
abstract:INTRODUCTION:In recent years, the anesthetized guinea pig has been used increasingly to evaluate the cardiovascular effects of drug-candidate molecules during lead optimization prior to conducting longer, more resource intensive safety pharmacology and toxicology studies. The aim of these studies was to evaluate the co...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2013.04.010
更新日期:2013-07-01 00:00:00
abstract::Hemodynamic and biochemical changes were studied on 36 white ELCO-rabbits, seven adult older than 150 days, seven immatures between 21 and 27 days, and seven neonatals between 7 and 14 days. Five supplementary hearts of each age group served for preischemic biochemical values. Protection during 60 min of global ischem...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(93)90016-8
更新日期:1993-12-01 00:00:00
abstract:INTRODUCTION:cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. METHODS:Total...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.02.001
更新日期:2004-07-01 00:00:00
abstract:INTRODUCTION:Drug-induced prolongation of the electrocardiographic QT interval (long QT syndrome) has been associated with increased risk of a serious ventricular arrhythmia, torsade de pointes. Inhibition of hERG, a cardiac potassium channel that controls action potential repolarization, is the most common cause of QT...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.10.004
更新日期:2009-01-01 00:00:00
abstract::High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESC...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106913
更新日期:2020-01-01 00:00:00
abstract::The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(96)00126-8
更新日期:1996-12-01 00:00:00
abstract:INTRODUCTION:The evaluation of drug disposition properties of chemical entities in drug discovery research typically involves the conduct of pharmacokinetic studies in rodents that requires blood sampling over several time points, preferably without disrupting the physiological status of the animals. Several blood with...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.05.006
更新日期:2007-09-01 00:00:00
abstract::Recently, Calderone and Martinotti (J Pharmacol Toxicol Meth 40:57-62, 1998) presented a simple equation for the estimation of agonist dissociation equilibrium constants from data obtained from receptor inactivation experiments using an irreversible, competitive antagonist. In the present paper, however, it is demonst...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(99)00011-8
更新日期:1998-11-01 00:00:00
abstract::The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concer...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 社论
doi:10.1016/j.vascn.2015.05.013
更新日期:2015-09-01 00:00:00