The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP)

2019 ◽  
pp. 106590 ◽  
Author(s):  
Jerónimo Auzmendi ◽  
Enes Akyuz ◽  
Alberto Lazarowski
Keyword(s):  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
Glycoprotein P ◽  
Kir Channels ◽  
P Glycoprotein ◽  
Inwardly Rectifying

scholarly journals Immunoreactivity of Muscarinic Acetylcholine M2 and Serotonin 5-HT2B Receptors, Norepinephrine Transporter and Kir Channels in a Model of Epilepsy

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 276
Author(s):  
Enes Akyuz ◽  
Zuleyha Doganyigit ◽  
Yam Nath Paudel ◽  
Betul Koklu ◽  
Emin Kaymak ◽  
...  
Keyword(s):  
K Channel ◽  
Neurotransmitter Receptors ◽  
Extracellular Potassium ◽  
Unexpected Death ◽  
Kir Channels ◽  
Ptz Kindling ◽  
Neurotransmitter Activity ◽  
K Concentration ◽  
Inwardly Rectifying

Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adult Wistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.

scholarly journals Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks

2010 ◽  
Vol 70 (3) ◽  
pp. 665-670 ◽  
Author(s):  
FA. Scorza ◽  
RM. Cysneiros ◽  
RM. Arida ◽  
VC. Terra ◽  
HR. Machado ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fish Consumption ◽  
Sudden Unexpected Death ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Unexpected Death ◽  
Positive Effects ◽  
Increased Risk ◽  
Fish And Shellfish

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

scholarly journals Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter

2021 ◽  
Author(s):  
Robert W. Robey ◽  
Andrea N. Robinson ◽  
Fatima Ali-Rahmani ◽  
Lyn M. Huff ◽  
Sabrina Lusvarghi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Multidrug Transporter ◽  
Glycoprotein P ◽  
Tissue Localization ◽  
Brain Vasculature ◽  
P Glycoprotein ◽  
Capillary Endothelial Cells ◽  
The Brain ◽  
Viable Model

ABSTRACTGiven its similarities with mammalian systems, the zebrafish has emerged as a potential model to study the blood-brain barrier (BBB). Capillary endothelial cells at the human BBB express high levels of P-glycoprotein (P-gp, encoded by the ABCB1 gene) and ABCG2 (encoded by the ABCG2 gene). However, little information has been available about ATP-binding cassette transporters expressed at the zebrafish BBB. In this study, we focus on the characterization and tissue localization of two genes that are similar to human ABCB1, zebrafish abcb4 and abcb5. Cytotoxicity assays with stably-transfected cell lines revealed that zebrafish Abcb5 cannot efficiently transport the substrates doxorubicin and mitoxantrone compared to human P-gp and zebrafish Abcb4. Additionally, zebrafish Abcb5 did not transport the fluorescent probes BODIPY-ethylenediamine or LDS 751, while they were readily transported by Abcb4 and P-gp. A high-throughput screen conducted with 90 human P-gp substrates confirmed that zebrafish Abcb4 has overlapping substrate specificity with P-gp. Basal ATPase activity of zebrafish Abcb4 and Abcb5 was comparable to that of human P-gp. In the brain vasculature, RNAscope probes to detect abcb4 colocalized with staining by the P-gp antibody C219, while abcb5 was not detected. Zebrafish abcb4 also colocalized with claudin-5 expression in brain endothelial cells. Abcb4 and Abcb5 had different tissue localizations in multiple zebrafish tissues, consistent with different functions. The data suggest that zebrafish Abcb4 most closely phenocopies P-gp and that the zebrafish may be a viable model to study the role of the multidrug transporter P-gp at the BBB.

scholarly journals Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Pierre-Francois Ceccaldi ◽  
Laurent Gavard ◽  
Laurent Mandelbrot ◽  
Elisabeth Rey ◽  
Robert Farinotti ◽  
...  
Keyword(s):  
Internal Control ◽  
Efflux Pump ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Glycoprotein P ◽  
Control Phase ◽  
P Glycoprotein ◽  
Ciclosporin A ◽  
High Albumin

Aims. To study the influence of P-glycoprotein (P-glycoprotein, ABCB1, MDR1) function on placental transfer of lopinavir with ritonavir at different albumin concentrations.Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L). After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes). Fetal Transfer Rate (FTR) and Clearance Index (CLI) were compared between the 2 phases.Results. In the control phase, the clearance index of lopinavir decreased from 0.401±0.058 to 0.007±0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L). When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [−0.156,−0.002],P=.046) and became positive for ritonavir.Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy.

A possible role of cyclooxygenase-2 in the relationship between sleep and sudden unexpected death in epilepsy

Epilepsia ◽  
2012 ◽  
Vol 53 (10) ◽  
pp. 1846-1848 ◽  
Author(s):  
Gabriela Matos ◽  
Laura Bennedsen ◽  
Vanessa A. Garcia ◽  
Fulvio A. Scorza ◽  
Esper A. Cavalheiro ◽  
...  
Keyword(s):  
Cyclooxygenase 2 ◽  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
The Relationship

Sudden, unexpected death and the role of the family physician.

1988 ◽  
Vol 6 (2) ◽  
pp. 176-187 ◽  
Author(s):  
William C. Wadland ◽  
Bert Keller ◽  
William Jones ◽  
James Chapados
Keyword(s):  
Family Physician ◽  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
The Family

The role of Mozart’s music in sudden unexpected death in epilepsy: A new open window of a dark room

2008 ◽  
Vol 12 (1) ◽  
pp. 208-209 ◽  
Author(s):  
Fulvio A. Scorza ◽  
Ricardo M. Arida ◽  
Marly de Albuquerque ◽  
Esper A. Cavalheiro
Keyword(s):  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
Open Window ◽  
Dark Room

scholarly journals Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3364 ◽  
Author(s):  
Bruno M. F. Gonçalves ◽  
David S. P. Cardoso ◽  
Maria-José U. Ferreira
Keyword(s):  
Multidrug Resistance ◽  
Natural Product ◽  
Abc Transporter ◽  
Efflux Pumps ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Multidrug Resistance Protein 1 ◽  
P Glycoprotein ◽  
Resistance Protein

Multidrug resistance (MDR) in cancer is one of the main limitations for chemotherapy success. Numerous mechanisms are behind the MDR phenomenon wherein the overexpression of the ATP-binding cassette (ABC) transporter proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein 1 (MRP1) is highlighted as a prime factor. Natural product-derived compounds are being addressed as promising ABC transporter modulators to tackle MDR. Flavonoids and terpenoids have been extensively explored in this field as mono or dual modulators of these efflux pumps. Nitrogen-bearing moieties on these scaffolds were proved to influence the modulation of ABC transporters efflux function. This review highlights the potential of semisynthetic nitrogen-containing flavonoid and terpenoid derivatives as candidates for the design of effective MDR reversers. A brief introduction concerning the major role of efflux pumps in multidrug resistance, the potential of natural product-derived compounds in MDR reversal, namely natural flavonoid and terpenoids, and the effect of the introduction of nitrogen-containing groups are provided. The main modifications that have been performed during last few years to generate flavonoid and terpenoid derivatives, bearing nitrogen moieties, such as aliphatic, aromatic and heterocycle amine, amide, and related functional groups, as well as their P-gp, MRP1 and BCRP inhibitory activities are reviewed and discussed.

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