Journal of pharmacological and toxicological methods最新文献

{"title":"Comparative assessment of Ca2+ oscillations in 2- and 3-dimensional hiPSC derived and isolated cortical neuronal networks","authors":"John P. Imredy ,&nbsp;Gautier Roussignol ,&nbsp;Holly Clouse ,&nbsp;Giorgia Salvagiotto ,&nbsp;Ludmilla Mazelin-Winum","doi":"10.1016/j.vascn.2023.107281","DOIUrl":"10.1016/j.vascn.2023.107281","url":null,"abstract":"<div><p>Human induced Pluripotent Stem Cell (hiPSC) derived neural cells offer great potential for modelling neurological diseases and toxicities and have found application in drug discovery and toxicology. As part of the European Innovative Medicines Initiative (IMI2) NeuroDeRisk (Neurotoxicity De-Risking in Preclinical Drug Discovery), we here explore the Ca²⁺ oscillation responses of 2D and 3D hiPSC derived neuronal networks of mixed Glutamatergic/GABAergic activity with a compound set encompassing both clinically as well as experimentally determined seizurogenic compounds. Both types of networks are scored against Ca²⁺ responses of a primary mouse cortical neuronal 2D network model serving as an established comparator assay. Parameters of frequency and amplitude of spontaneous global network Ca²⁺ oscillations and the drug-dependent directional changes to these were assessed, and predictivity of seizurogenicity scored using contingency table analysis. In addition, responses between models were compared between both 2D models as well as between 2D and 3D models. Concordance of parameter responses was best between the hiPSC neurospheroid and the mouse primary cortical neuron model (77% for frequency and 65% for amplitude). Decreases in spontaneous Ca²⁺ oscillation frequency and amplitude were found to be the most basic shared determinants of risk of seizurogenicity between the mouse and the neurospheroid model based on testing of clinical compounds with documented seizurogenic activity. Increases in spontaneous Ca²⁺ oscillation frequency were primarily observed with the 2D hIPSC model, though the specificity of this effect to seizurogenic clinical compounds was low (33%), while decreases to spike amplitude in this model were more predictive of seizurogenicity. Overall predictivities of the models were similar, with sensitivity of the assays typically exceeding specificity due to high false positive rates. Higher concordance of the hiPSC 3D model over the 2D model when compared to mouse cortical 2D responses may be the result of both a longer maturation time of the neurospheroid (84–87 days for 3D vs. 22–24 days for 2D maturation) as well as the 3-dimensional nature of network connections established. The simplicity and reproducibility of spontaneous Ca²⁺ oscillation readouts support further investigation of hiPSC derived neuronal sources and their 2- and 3-dimensional networks for neuropharmacological safety screening.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107281"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1056871923000321/pdfft?md5=946c7fa1a3bb017891f56e896414770e&pid=1-s2.0-S1056871923000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9970688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common chemistry, manufacturing, and control deficiencies in abbreviated new drug applications assessed by the US Food and drug administration: Hurdle to access cost-effective medicines","authors":"Samruddhi B. Kulkarni ,&nbsp;Vinod L. Gaikwad","doi":"10.1016/j.vascn.2023.107295","DOIUrl":"10.1016/j.vascn.2023.107295","url":null,"abstract":"<div><p>To market a generic product in the United States, it must be registered in Common Technical Document (CTD) format with the US Food and Drug Administration. The Generic Drug User Fee Act went into force in 2012, to expedite the timely review of Abbreviated New Drug Applications (ANDA) by communicating potential defects in the application to the applicant through deficiency letters at different time intervals during the review cycle. This often delays product approval since these deficiencies must be resolved before the product can be approved. In the present study, a study was performed to analyze the recurrent queries for ANDA applications in the CTD quality module from 2013 to 2020, and the probable corrective and preventive action to be taken was drafted. The most frequently occurring queries were observed in the sections titled “Description of manufacturing process and process controls”, “Controls of critical steps and intermediates”, “Specifications (Control of drug product)”, and “Stability data”.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107295"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the sensitivity of cross-over and parallel study designs for QTc assessment: An analysis based on a single large study of moxifloxacin in 48 nonhuman primates","authors":"Derek J. Leishman ,&nbsp;David L. Holdsworth ,&nbsp;Derek D. Best ,&nbsp;Brian M. Roche","doi":"10.1016/j.vascn.2023.107299","DOIUrl":"10.1016/j.vascn.2023.107299","url":null,"abstract":"<div><p><span>The cardiovascular safety pharmacology (SP) study conducted to satisfy ICH S7A and S7B has commonly used a cross-over study design where each animal receives all treatments. In an increasing number of cases, cross-over designs are not possible and parallel studies have to be used. These can seldom be as large as 8 animals/treatment to match an </span><em>n</em> = 8 cross-over. Animals in parallel designs receive only one treatment. Parallel studies will have a different sensitivity to detect changes. This sensitivity is a critical question in using nonclinical QTc evaluations to support an integrated proarrhythmic risk assessment under the newly released ICH E14/S7B Q&amp;As. The current analysis used a study large enough (<em>n</em> = 48) to be analyzed both as a parallel and as a cross-over design to directly compare the performance of the two experimental designs coupled to different statistical models, while all other study conduct aspects were the same.</p><p><span>A total of 48 nonhuman primates (NHP) received 2 different treatments twice: vehicle, moxifloxacin (80 mg/kg), vehicle, moxifloxacin (80 mg/kg). Post-dose QTc interval data were recorded for 48 h for each treatment. Data were analyzed using 12 animals randomly selected for each treatment in a parallel design or as an </span><em>n</em> = 48 animal cross-over study. Different statistical models were used. The primary endpoint was the residual deviation (sigma) from the models applied to hourly time intervals. The sigma was used to determine the minimal detectable difference (MDD) for the study design-statistical model combination.</p><p>Two statistical models were applicable to either study design. They gave similar sigma and resulting MDD values. In cross-over designs, the individual animal identification (ID) can be used in the statistical model. This enabled the smallest MDD value. Simple statistical models for analysis were identified: Treatment + Baseline for parallel designs and Treatment + ID for cross-over designs.</p><p>The statistical sensitivity of NHP parallel study designs is reasonable (MDD for <em>n</em> = 6 of 12.7 ms), and in combination with testing exposures higher than likely to be necessary in man could be used in an integrated risk assessment. Where sensitivity of the NHP in vivo QTc assessment is critical, the cross-over design enabled a higher sensitivity (MDD 12.2 ms for <em>n</em> = 4; 8 ms for <em>n</em> = 8).</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107299"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hERG agonists pose challenges to web-based machine learning methods for prediction of drug-hERG channel interaction","authors":"Aziza El Harchi,&nbsp;Jules C. Hancox","doi":"10.1016/j.vascn.2023.107293","DOIUrl":"10.1016/j.vascn.2023.107293","url":null,"abstract":"<div><p>Pharmacological blockade of the I_Kr channel (hERG) by diverse drugs in clinical use is associated with the Long QT Syndrome that can lead to life threatening arrhythmia. Various computational tools including machine learning models (MLM) for the prediction of hERG inhibition have been developed to facilitate the throughput screening of drugs in development and optimise thus the prediction of hERG liabilities. The use of MLM relies on large libraries of training compounds for the quantitative structure-activity relationship (QSAR) modelling of hERG inhibition. The focus on inhibition omits potential effects of hERG channel agonist molecules and their associated QT shortening risk. It is instructive, therefore, to consider how known hERG agonists are handled by MLM. Here, two highly developed online computational tools for the prediction of hERG liability, Pred-hERG and HergSPred were probed for their ability to detect hERG activator drug molecules as hERG interactors. In total, 73 hERG blockers were tested with both computational tools giving overall good predictions for hERG blockers with reported IC₅₀s below Pred-hERG and HergSPred cut-off threshold for hERG inhibition. However, for compounds with reported IC₅₀s above this threshold such as disopyramide or sotalol discrepancies were observed. HergSPred identified all 20 hERG agonists selected as interacting with the hERG channel. Further studies are warranted to improve online MLM prediction of hERG related cardiotoxicity, by explicitly taking into account channel agonism as well as inhibition.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107293"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation of closed-chest infarction porcine model to adult Pannon minipigs","authors":"Dénes Kőrösi ,&nbsp;András Vorobcsuk ,&nbsp;Dániel Fajtai ,&nbsp;Ottó Tátrai ,&nbsp;Emőke Bodor ,&nbsp;Kornélia Farkas ,&nbsp;Rita Garamvölgyi","doi":"10.1016/j.vascn.2023.107469","DOIUrl":"10.1016/j.vascn.2023.107469","url":null,"abstract":"<div><p>The aim of the recent study was to collect data on the genotype characteristics of the Hungarian self-bred Pannon minipigs by adapting a standardized infarct model procedure. Closed chest AMI was induced by balloon occlusion for 90 min in the left anterior descendent coronary artery (LAD) in 24 adult intact female minipigs followed by reperfusion. To assess the left ventricular (LV) function, serial cardiac magnetic resonance imaging (cMRI) was performed prior to the experimental procedure, on day 3 post-AMI (72 ± 12 h), and at 1 month follow-up (Day 30 ± 2 days). Compared to baseline cMRI scans the end-diastolic volume (EDV) was increased on days 3 and 30 On day 3 the left ventricular ejection fraction (LVEF) decreased significantly but there was no statistical difference between the baseline and day 30 measurements. Cardiac output, stroke volume, and end-systolic volume significantly were increased compared to baseline on day 30 A high percentage (54%) of malignant arrhythmias occurred during the AMI procedure, with a 25% mortality rate. The compensatory capacity of the Pannon minipig heart is excellent therefore the use of different cardiac parameters and invasive measurements is advisable in chronic pharmacological experiments to complement cMRI data.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107469"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10450383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-target pharmacological activity at various kinases: Potential functional and pathological side effects","authors":"Jonathon R. Green ,&nbsp;Prathap Kumar S. Mahalingaiah ,&nbsp;Sujatha M. Gopalakrishnan ,&nbsp;Michael J. Liguori ,&nbsp;Scott W. Mittelstadt ,&nbsp;Eric A.G. Blomme ,&nbsp;Terry R. Van Vleet","doi":"10.1016/j.vascn.2023.107468","DOIUrl":"10.1016/j.vascn.2023.107468","url":null,"abstract":"<div><p>In drug discovery, during the lead optimization and candidate characterization stages, novel small molecules are frequently evaluated in a battery of in vitro pharmacology assays to identify potential unintended, off-target interactions with various receptors, transporters, ion channels, and enzymes, including kinases. Furthermore, these screening panels may also provide utility at later stages of development to provide a mechanistic understanding of unexpected safety findings. Here, we present a compendium of the most likely functional and pathological outcomes associated with interaction(s) to a panel of 95 kinases based on an extensive curation of the scientific literature. This panel of kinases was designed by AbbVie based on safety-related data extracted from the literature, as well as from over 20 years of institutional knowledge generated from discovery efforts. For each kinase, the scientific literature was reviewed using online databases and the most often reported functional and pathological effects were summarized. This work should serve as a practical guide for small molecule drug discovery scientists and clinical investigators to predict and/or interpret adverse effects related to pharmacological interactions with these kinases.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107468"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of bioanalysis of dried blood samples","authors":"Elham Ataei Alizadeh ,&nbsp;Georg Rast ,&nbsp;Chris Cantow ,&nbsp;Jessica Schiwon ,&nbsp;Florian Krause ,&nbsp;Guido R.Y. De Meyer ,&nbsp;Pieter-Jan Guns ,&nbsp;Brian D. Guth ,&nbsp;Michael Markert","doi":"10.1016/j.vascn.2023.107296","DOIUrl":"10.1016/j.vascn.2023.107296","url":null,"abstract":"<div><h3>Introduction</h3><p>Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape.</p></div><div><h3>Methods</h3><p>Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples.</p></div><div><h3>Results</h3><p>With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques.</p></div><div><h3>Discussion</h3><p>Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107296"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Appraisal of state-of-the-art” The 2021 Distinguished Service Award of the Safety Pharmacology Society: Reflecting on the past to tackle challenges ahead","authors":"Jean-Pierre Valentin,&nbsp;Alicia Sibony,&nbsp;Marie-Luce Rosseels,&nbsp;Annie Delaunois","doi":"10.1016/j.vascn.2023.107269","DOIUrl":"10.1016/j.vascn.2023.107269","url":null,"abstract":"<div><p>This appraisal of state-of-the-art manuscript highlights and expands upon the thoughts conveyed in the lecture of Dr. Jean-Pierre Valentin, recipient of the 2021 Distinguished Service Award of the Safety Pharmacology<span> Society, given on the 2nd December 2021. The article reflects on the strengths, weaknesses, opportunities, and threats that surrounded the evolution of safety and secondary pharmacology over the last 3 decades with a particular emphasis on pharmaceutical drug development delivery, scientific and technological innovation, complexities of regulatory framework and people leadership and development. The article further built on learnings from past experiences to tackle constantly emerging issues and evolving landscape whilst being cognizant of the challenges facing these disciplines in the broader drug development and societal context.</span></p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107269"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of the bioanalytical methods used for the determination of benzodiazepines in biological samples and their suitability for emergency toxicological analysis","authors":"Mohamed Yafout,&nbsp;Rachid Aït Mouss,&nbsp;Houda Bouchafra,&nbsp;Lhoussaine Zarayby,&nbsp;Ibrahim Sbai El-Otmani","doi":"10.1016/j.vascn.2023.107294","DOIUrl":"10.1016/j.vascn.2023.107294","url":null,"abstract":"<div><p>Benzodiazepines are one of the most widely used classes of drugs around the world. They are medically used in different therapeutic areas including insomnia, anxiety, epilepsy, and anesthesia. Unfortunately, these drugs are very widespread in the illicit market for recreational purposes and cause drug dependence, traffic accidents, and criminality. Furthermore, benzodiazepine misuse leads to acute poisoning cases that often end up in hospital emergency rooms. Therefore, it is crucial for hospitals to possess straightforward and efficient bioanalytical techniques that enable the swift detection of benzodiazepines in biological samples. This review provides a general overview of the different bioanalytical techniques used for the detection and quantification of benzodiazepines in biological samples and emphasizes their suitability for emergency toxicological analyzes.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"123 ","pages":"Article 107294"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9865102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation","authors":"Nidhi Tiwari ,&nbsp;Abhinav Jaimini ,&nbsp;Gaurav Kumar Jain ,&nbsp;Geeta Aggarwal ,&nbsp;Gaurav Mittal","doi":"10.1016/j.vascn.2023.107280","DOIUrl":"https://doi.org/10.1016/j.vascn.2023.107280","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a ‘priority neglected tropical disease’ and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely &lt;sup&gt;99m&lt;/sup&gt;Tc-Sulfur colloid (SC), &lt;sup&gt;99m&lt;/sup&gt;Tc-Phytate (Phy) and &lt;sup&gt;99m&lt;/sup&gt;Tc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29–1.48 MBq in 100 μl normal saline) of either &lt;sup&gt;99m&lt;/sup&gt;Tc-Phy/ &lt;sup&gt;99m&lt;/sup&gt;Tc-SC/ &lt;sup&gt;99m&lt;/sup&gt;Tc-HSA into the tail as ‘mock-venom’. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% &lt;em&gt;w&lt;/em&gt;/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. &lt;sup&gt;99m&lt;/sup&gt;Tc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of &lt;sup&gt;99m&lt;/sup&gt;Tc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (&lt;em&gt;P&lt;/em&gt; &lt; 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, &lt;sup&gt;99m&lt;/sup&gt;Tc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to &lt;sup&gt;99m&lt;/sup&gt;Tc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that &lt;sup&gt;99m&lt;/sup&gt;Tc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a si","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"122 ","pages":"Article 107280"},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50197553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}