scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

2021 ◽  
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
The Future ◽  
In Silico Models

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

Sci ◽  
2021 ◽  
Vol 3 (4) ◽  
pp. 45
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
Animal Testing ◽  
The Future

Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

Understanding the past, getting prepared for the future. (Going from in vivo to in vitro to in silico)

2021 ◽  
Vol 17 (10) ◽  
pp. 787-789
Author(s):  
Patrick W. Serruys ◽  
Ahmed Elkoumy ◽  
Osama Soliman
Keyword(s):  
In Silico ◽  
The Past ◽  
The Future

scholarly journals Antiurolithiatic Evaluation of α- Mangostin Fraction Isolated from Garcinia mangostana Pericarp through Computational, in vitro and in vivo Approach

2021 ◽  
pp. 63-78
Author(s):  
Akash Kumaran ◽  
Prabhu Sukumaran
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Animal Studies ◽  
Oxalate Oxidase ◽  
Garcinia Mangostana ◽  
Molecular Docking Study ◽  
Group I ◽  
Fruit Pericarp

Background: The aqueous crude extract of Garcinia mangostana fruit pericarp was already proven to contain antiurolithiatic property. Based on this previous study the current study was focused on analysing the anti-urolithiatic property of α- mangostin, a xanthone polyphenol isolated from the fruit pericarp of G. manostana, which has not been tested for its anti-urolithiatic property till now. Objective: The aim of this present study is to evaluate the anti-urolithiatic property of the isolated α- mangostin from G. mangostana fruit pericarp using in silico, in vitro and in vivo analysis. Study Design: Antiurolithiatic activity of α- mangostin through Molecular docking study à In vitro S.S.M model study à Animal studies. Place and Duration: Department of Biotechnology, Sri Venkateswara College of Engineering, Post Bag No.1, Pennalur, Sriperumbudur Tk, Kancheepuram Dt, TN-602117, India. Materials and Methods: In silico Molecular docking of α- mangostin with Kidney stone forming proteins- Xanthine dehydrogenase (Xdh), Oxalate oxidase and Tamm-Horesefall Protein (THP) were performed using AutoDock 4.0 and was visualised in Discovery studio software. In vitro Simultaneous Static flow Model (S.S.M) was performed to investigate its Antiurolithiatic property against Calcium Oxalate (CaOx) and Calcium Phosphate (CaP) crystals. Based on the in silico and in vitro analysis, the study was extrapolated to Ethylene Glycol (EG) induced urolithiasis rat models. The animal study was performed with 36 Albino Wistar rats which were divided into 6 groups. All group except group I received EG (0.75% in drinking water) for the induction of Urolithiasis for 28 days under curative regimen. Group III was administered orally with Cystone (750 mg/kg) from 15th to 28thday. Group IV to VI was administered orally with GMPE (300 mg/kg, 500 mg/kg and 750 mg/kg) from 15thto 28th day. Results: Molecular Docking studies showed an inhibitory interaction of α- mangostin with oxalate oxidase, Xdh and THP with binding affinity of -4.47, -4.00 and -3.41 Kcal/mol respectively. S.S.M showed 54.71% inhibition for CaOx crystals and 62.21% inhibition of CaP crystals. The animal studies showed significant results in reduction of serum calcium (P<0.01), serum phosphate (P<0.01), urine calcium(P<0.001) and urine phosphate(P<0.01). Conclusion: Thus, α- mangostin proved to be potent Anti-urolithiatic agent by reducing and disintegrating the urinary crystals.

scholarly journals Heat Shock Protein 72 Expressing Stress in Sepsis: Unbridgeable Gap between Animal and Human Studies—A Hypothetical “Comparative” Study

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
George Briassoulis ◽  
Efrossini Briassouli ◽  
Diana-Michaela Fitrolaki ◽  
Ioanna Plati ◽  
Kleovoulos Apostolou ◽  
...  
Keyword(s):  
Heat Shock ◽  
Animal Models ◽  
Heat Shock Protein ◽  
Comparative Study ◽  
Protective Effect ◽  
Animal Studies ◽  
Human Studies ◽  
Heat Shock Protein 72

Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical “comparative study” model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P<0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P<0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P<0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P<0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.

scholarly journals Self-similar synchronization of calcium and membrane potential transitions during AP cycles predict HR across species

2020 ◽  
Author(s):  
Syevda Tagirova Sirenko ◽  
Kenta Tsutsui ◽  
Kirill Tarasov ◽  
Dongmei Yang ◽  
Ashley N Wirth ◽  
...  
Keyword(s):  
Heart Rate ◽  
Animal Models ◽  
Animal Studies ◽  
Power Laws ◽  
Single Species ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
Self Similar

AbstractBackgroundTranslation of knowledge of sinoatrial nodal “SAN” automaticity gleaned from animal studies to human dysrhythmias, e.g. “Sick Sinus” Syndrome (SSS) requiring electronic pacemaker insertion has been sub-optimal, largely because heart rate (HR) varies widely across species.ObjectivesTo discover regulatory universal mechanisms of normal automaticity in SAN pacemaker cells that are self-similar across species.MethodSub-cellular Ca2+ releases, whole cell AP-induced Ca2+ transients and APs were recorded in isolated mouse, guinea-pig, rabbit and human SAN cells. Parametric Ca2+ and Vm Kinetic Transitions (PCVKT) during phases of AP cycles from their ignition to recovery were quantified.ResultsAlthough both action potential cycle lengths (APCL) and PCVKT during AP cycles differed across species by ten-fold, trans-species scaling of PCVKT during AP cycles and scaling, of PCVKT to APCL in cells in vitro, EKG RR intervals in vivo, and BM were self-similar (obeyed power laws) across species. Thus, APCL in vitro, HR in vivo, and BM of any species can be predicted by PCVKT during AP cycles in SAN cells measured in any single species in vitro.ConclusionsIn designing optimal HR to match widely different BM and energy requirements from mice to humans, nature did not “reinvent pacemaker cell wheels”, but differentially scaled kinetics of gears that regulate the rates at which the “wheels spin”. This discovery will facilitate the development of novel pharmalogic therapies and biologic pacemakers featuring a normal, wide-range rate regulation in animal models and the translation of these to humans to target recalcitrant human SSS.Condensed AbstractStudies in animal models are an important facet of cardiac arrhythmia research. Because HR differs by over ten-fold between some animals and humans, translation of knowledge about regulatory mechanisms of SAN normal automaticity gleaned from studies in animal models to target human SSS has been sub-optimal. Our findings demonstrating that trans-species self-similarity of sub-cellular and cellular mechanisms that couple Ca2+ to Vm during AP cycles can predict heart rate in vivo from mice to humans will inform on the design of novel studies in animal models and facilitate translation of this knowledge to target human disease.

scholarly journals Current model systems for the study of preeclampsia

2018 ◽  
Vol 243 (6) ◽  
pp. 576-585 ◽  
Author(s):  
ML Martinez-Fierro ◽  
GP Hernández-Delgadillo ◽  
V Flores-Morales ◽  
E Cardenas-Vargas ◽  
M Mercado-Reyes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
In Silico ◽  
Complex Disease ◽  
Model Systems ◽  
Trophoblast Invasion ◽  
Wide Range ◽  
In Silico Models

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal–fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein–protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

Sign in / Sign up

Export Citation Format

Share Document