scholarly journals The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice

2019 ◽  
Vol Volume 14 ◽  
pp. 5595-5609 ◽  
Author(s):  
Cai-Xia Lin ◽  
Jing-Li Gu ◽  
Ji-Min Cao
Keyword(s):  
Ion Channels ◽  
Platinum Nanoparticles ◽  
Heart Rhythm ◽  
Toxic Effects ◽  
Transmembrane Potentials ◽  
Acute Toxic

scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

scholarly journals Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1716
Author(s):  
Kun Tong ◽  
Ruotian Zhang ◽  
Fengzhi Ren ◽  
Tao Zhang ◽  
Junlin He ◽  
...  
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Formalin Test ◽  
Sodium Ion ◽  
Inhibitory Potency ◽  
Voltage Gated ◽  
Patch Clamp Electrophysiology ◽  
Sodium Ion Channels

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.

Effect of hemorrhagic shock on hepatic transmembrane potentials and intracellular electrolytes, in vivo

1981 ◽  
Vol 240 (3) ◽  
pp. R211-R219 ◽  
Author(s):  
M. M. Sayeed ◽  
R. J. Adler ◽  
I. H. Chaudry ◽  
A. E. Baue
Keyword(s):  
Hemorrhagic Shock ◽  
Cell Volume ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Shed Blood ◽  
Average Value ◽  
Transmembrane Potentials ◽  
Relative Membrane Permeability

In this study we investigated in vivo changes in hepatic cellular electrolytes and resting transmembrane potentials (Em) during hemorrhagic shock. Hepatic Na-K transport and cell volume regulation were assessed in vitro. Rats were bled and the ensuing hypotension (40 mmHg) was maintained by returning 25-30% (intermediate-shock, IS) or 55-60% (late-shock, LS) of the shed blood. We resuscitated IS rats by reinfusion of all of the remaining shed blood and Ringer's lactate solution. Hepatic cellular Na and Cl increased and K decreased progressively with shock. Resuscitation of IS rats restored cell K and Cl but not Na to preshock levels. Em decreased from the control average value of -40 (mV) to -31 in IS and -19 in LS. Em was partially restored (-36 mV) after resuscitation. We evaluated changes in relative membrane permeability to Na and K (PNa/PK) with shock by assuming Em either to be a Na-K exchange diffusion potential or due to an unequally coupled movement of Na and K. These evaluations show a lack of effect of shock (IS, with or without resuscitation) on PNa/PK. Our observations are compatible with failure of an electrogenic Na pump in shock. This may be related to loss of hepatic cell volume regulation in shock.

scholarly journals ADME/Tox Properties and Biochemical Interactions of Silybin Congeners: In silico Study

2017 ◽  
Vol 12 (2) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Antonia Diukendjieva ◽  
Merilin Al Sharif ◽  
Petko Alov ◽  
Tania Pencheva ◽  
Ivanka Tsakovska ◽  
...  
Keyword(s):  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Estrogenic Activity ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Toxic Effects ◽  
Active Constituent ◽  
Main Component

Silymarin, the active constituent of Silybum marianum (milk thistle), and its main component, silybin, are products with well-known hepatoprotective, cytoprotective, antioxidant, and chemopreventative properties. Despite substantial in vitro and in vivo investigations of these flavonolignans, their mechanisms of action and potential toxic effects are not fully defined. In this study we explored important ADME/Tox properties and biochemical interactions of selected flavonolignans using in silico methods. A quantitative structure–activity relationship (QSAR) model based on data from a parallel artificial membrane permeability assay (PAMPA) was used to estimate bioavailability after oral administration. Toxic effects and metabolic transformations were predicted using the knowledge-based expert systems Derek Nexus and Meteor Nexus (Lhasa Ltd). Potential estrogenic activity of the studied silybin congeners was outlined. To address further the stereospecificity of this effect the stereoisomeric forms of silybin were docked into the ligand-binding domain of the human estrogen receptor alpha (ERα) (MOE software, CCG). According to our results both stereoisomers can be accommodated into the ERα active site, but different poses and interactions were observed for silybin A and silybin B.

scholarly journals Sensing through Non-Sensing Ocular Ion Channels

2020 ◽  
Vol 21 (18) ◽  
pp. 6925
Author(s):  
Meha Kabra ◽  
Bikash Ranjan Pattnaik
Keyword(s):  
Ion Channels ◽  
Visual Processing ◽  
Signal Transmission ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Cone Dystrophy ◽  
Wide Range ◽  
The Impact

Ion channels are membrane-spanning integral proteins expressed in multiple organs, including the eye. In the eye, ion channels are involved in various physiological processes, like signal transmission and visual processing. A wide range of mutations have been reported in the corresponding genes and their interacting subunit coding genes, which contribute significantly to an array of blindness, termed ocular channelopathies. These mutations result in either a loss- or gain-of channel functions affecting the structure, assembly, trafficking, and localization of channel proteins. A dominant-negative effect is caused in a few channels formed by the assembly of several subunits that exist as homo- or heteromeric proteins. Here, we review the role of different mutations in switching a “sensing” ion channel to “non-sensing,” leading to ocular channelopathies like Leber’s congenital amaurosis 16 (LCA16), cone dystrophy, congenital stationary night blindness (CSNB), achromatopsia, bestrophinopathies, retinitis pigmentosa, etc. We also discuss the various in vitro and in vivo disease models available to investigate the impact of mutations on channel properties, to dissect the disease mechanism, and understand the pathophysiology. Innovating the potential pharmacological and therapeutic approaches and their efficient delivery to the eye for reversing a “non-sensing” channel to “sensing” would be life-changing.

In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes

2019 ◽  
Vol 48 (18) ◽  
pp. 6026-6039 ◽  
Author(s):  
Vivianne S. Velozo-Sá ◽  
Luciano R. Pereira ◽  
Aliny P. Lima ◽  
Francyelli Mello-Andrade ◽  
Manuela R. M. Rezende ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Larval Development ◽  
In Vitro Cytotoxicity ◽  
Toxic Effects ◽  
Toxicity Evaluation ◽  
Embryonic And Larval Development

Ru(ii)/2-mercaptopyrimidine complexes active against cancer cells did not present toxic effects during embryonic and larval development of zebrafish.

scholarly journals Comparison of the in vitro and in vivo toxic effects of thymoquinone using oral cancer HSC-3 and HSC-4 cell lines, oral fibroblasts, HACAT cell line, and Zebrafish embryos

2019 ◽  
Vol 16 ◽  
pp. 2108-2114
Author(s):  
Wastuti Hidayati Suriyah ◽  
Abdul Razak Kasmuri ◽  
Fiona How Ni Foong ◽  
Dhona Afriza ◽  
Solachuddin Jauhari Arief Ichwan
Keyword(s):  
Oral Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Hacat Cell ◽  
Toxic Effects ◽  
Zebrafish Embryos ◽  
Hacat Cell Line

Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue

2012 ◽  
Vol 44 (4) ◽  
pp. 245-258 ◽  
Author(s):  
Jane Synnergren ◽  
Caroline Améen ◽  
Andreas Jansson ◽  
Peter Sartipy
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Human Heart ◽  
Embryonic Stem ◽  
Heart Tissue ◽  
Phenotypic Characterization ◽  
Adult Heart ◽  
Promising Source

It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca2+-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiac-related ion channels and Ca2+-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.

The Reactivating and Therapeutic Efficacy of Oximes to Counteract Russian VX Poisonings

2006 ◽  
Vol 25 (5) ◽  
pp. 397-401 ◽  
Author(s):  
Jiri Kassa ◽  
Daniel Jun ◽  
Kamil Kuca
Keyword(s):  
Therapeutic Efficacy ◽  
Central Compartment ◽  
Toxic Effects ◽  
Peripheral Compartment ◽  
Structural Analogue ◽  
Hi 6 ◽  
Alkyl Groups ◽  
Brain Acetylcholinesterase ◽  
Acute Toxic

Russian VX ( O-isobutyl- S-(2-diethylaminoethyl)methylphosphonothioate) is the structural analogue of VX agent. It differs from VX agent ( O-ethyl- S-(2-diisopropylaminoethyl) methylphosphonothioate) by two alkyl groups. The potency of currently available oximes (pralidoxime, obidoxime, HI-6) to reactivate Russian VX–inhibited acetylcholinesterase and to eliminate Russian VX–induced acute toxic effects was evaluated using in vivo methods. In vivo determined percentage of reactivation of Russian VX–inhibited blood and brain acetylcholinesterase in poisoned rats shows that HI-6 seems to be the most efficacious reactivator of Russian VX–inhibited acetylcholinesterase among currently used oximes in the peripheral compartment, whereas no difference between reactivating efficacy of all tested oximes was observed in the central compartment. The oxime HI-6 was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in Russian VX–poisoned mice among all studied oximes. Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings.

Evidence that signal transduction for osmoreception is mediated by stretch-activated ion channels in tilapia

2003 ◽  
Vol 284 (5) ◽  
pp. C1290-C1296 ◽  
Author(s):  
A. P. Seale ◽  
N. H. Richman ◽  
T. Hirano ◽  
I. Cooke ◽  
E. G. Grau
Keyword(s):  
Ion Channels ◽  
Channel Blocker ◽  
Oreochromis Mossambicus ◽  
Cell Swelling ◽  
Simultaneous Measurements ◽  
Perfusion Chamber ◽  
Intracellular Ca ◽  
Stretch Activated Ion Channels

Prolactin (PRL) plays a central role in the freshwater osmoregulation of teleost fish, including the tilapia ( Oreochromis mossambicus). Consistent with this action, PRL release from the tilapia pituitary increases as extracellular osmolality is reduced both in vitro and in vivo. Dispersed tilapia PRL cells were incubated in a perfusion chamber that allowed simultaneous measurements of cell volume and PRL release. Intracellular Ca2+ concentrations were measured from fura 2-loaded PRL cells treated in a similar way. Gadolinium (Gd3+), known to block stretch-activated cation channels, inhibited hyposmotically induced PRL release in a dose-related manner without preventing cell swelling. Nifedipine, an L-type Ca2+ channel blocker, did not prevent the increase in PRL release during hyposmotic stimulation. A high, depolarizing concentration of KCl induced a transient and marked increase of intracellular Ca2+ and release of PRL but did not prevent the rise in intracellular Ca2+ and PRL release evoked by exposure to hyposmotic medium. These findings suggest that a decrease in extracellular osmolality stimulates PRL release through the opening of stretch-activated ion channels, which allow extracellular Ca2+ to enter the cell when it swells.

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