Differential Sensitivity of Two Endothelial Cell Lines to Hydrogen Peroxide Toxicity: Relevance for In Vitro Studies of the Blood–Brain Barrier

Alamu, Olufemi A.; Rado, Mariam; Ekpo, Okobi Eko; Fisher, David

doi:10.3390/cells9020403

Cited by 14 publications

(9 citation statements)

References 53 publications

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“…The relevance of oxidative stress and advantages/disadvantages of different experimental models used, especially in vitro, to study human pathophysiology was further stressed by O. Alamu et al, who analyzed the relevance of differential sensitivity of different endothelial cell lines to hydrogen peroxide used for in vitro studies of the blood-brain barrier (BBB) [8]. The authors found that even standardized and well-known cell lines can substantially differ in their antioxidant characteristics.…”

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confidence: 99%

Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

Žarković

2020

Cells

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Our common knowledge on oxidative stress has evolved substantially over the years, being focused mostly on the fundamental chemical reactions and the most relevant chemical species involved in human pathophysiology of oxidative stress-associated diseases. Thus, reactive oxygen species and reactive nitrogen species (ROS and RNS) were identified as key players in initiating, mediating, and regulating the cellular and biochemical complexity of oxidative stress either as physiological (acting pro-hormetic) or as pathogenic (causing destructive vicious circles) processes. The papers published in this particular Special Issue of Cells show an impressive range on the pathophysiological relevance of ROS and RNS, including the relevance of second messengers of free radicals like 4-hydroxynonenal, allowing us to assume that the future will reveal even more detailed mechanisms of their positive and negative effects that might improve the monitoring of major modern diseases, and aid the development of advanced integrative biomedical treatments.

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confidence: 99%

Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

Žarković

2020

Cells

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“…Additionally, this in-vitro human BBB model correlated well with human pharmacokinetic parameters 34 . We also have the advantage of the use of nonimmortalized cells, since immortalized cell lines have accumulated mutations, mycoplasma contamination, loss of BBB-like phenotype and authenticity complications 75,76 , resulting in varying BBB characteristics between intraspecies endothelial cell lines 77 .…”

Section: Discussionmentioning

confidence: 99%

Endothelial iron homeostasis regulates BBB integrity via the HIF2α – Ve-cadherin pathway

Rand

Ravid

Atrakchi

et al. 2020

Preprint

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The blood-brain barrier serves as the guardian of the CNS, tightly regulating the movement of ions, molecules, and cells between the circulatory system and brain. We have used an in-vitro BBB injury model to gain a better understanding of the mechanisms controlling BBB integrity. This model exposes a co-culture of human stem-cell derived brain-like endothelial cells and brain pericytes that mimic the BBB, to the organophosphate paraoxon. This exposure results in rapid lipid peroxidation, initiating a ferroptosis-like process. Additionally, mitochondrial ROS formation (MRF) and increase in mitochondrial membrane permeability, were also detected leading to apoptotic cell death. Yet, these processes do not directly result in damage to barrier functionality since blocking them does not reverse the increased permeability. We found that the iron chelator, Desferal© significantly decreases MRF and apoptosis subsequent to paraoxon exposure, while also rescuing barrier integrity by inhibiting the liable iron pool increase, inducing HIF2α expression and preventing the degradation of Ve-cadherin on the cell surface. Moreover, the novel nitroxide JP4-039 significantly rescues both injury-induced endothelium cell toxicity and barrier functionality.

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“…A recent study investigated how BBB endothelial cells respond to oxidative stress by exposing b.End3 and b.End5 cell lines to hydrogen peroxide. [ 59 ]. A decreasing viability of both cell line following exposure to increasing concentrations of hydrogen peroxide was shown.…”

Section: Cell Cultures As In Vitro Bbb Modelsmentioning

confidence: 99%

Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies

Monteiro,

Barbosa,

Remião

et al. 2024

Biomedicines

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The biological barriers existing in the human body separate the blood circulation from the interstitial fluid in tissues. The blood–brain barrier (BBB) isolates the central nervous system from the bloodstream, presenting a dual role: the protection of the human brain against potentially toxic/harmful substances coming from the blood, while providing nutrients to the brain and removing metabolites. In terms of architectural features, the presence of junctional proteins (that restrict the paracellular transport) and the existence of efflux transporters at the BBB are the two major in vivo characteristics that increase the difficulty in creating an ideal in vitro model for drug permeability studies and neurotoxicity assessments. The purpose of this work is to provide an up-to-date literature review on the current in vitro models used for BBB studies, focusing on the characteristics, advantages, and disadvantages of both primary cultures and immortalized cell lines. An accurate analysis of the more recent and emerging techniques implemented to optimize the in vitro models is also provided, based on the need of recreating as closely as possible the BBB microenvironment. In fact, the acceptance that the BBB phenotype is much more than endothelial cells in a monolayer has led to the shift from single-cell to multicellular models. Thus, in vitro co-culture models have narrowed the gap between recreating as faithfully as possible the human BBB phenotype. This is relevant for permeability and neurotoxicity assays, and for studies related to neurodegenerative diseases. Several studies with these purposes will be also presented and discussed.

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Differential Sensitivity of Two Endothelial Cell Lines to Hydrogen Peroxide Toxicity: Relevance for In Vitro Studies of the Blood–Brain Barrier

Cited by 14 publications

References 53 publications

Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

Endothelial iron homeostasis regulates BBB integrity via the HIF2α – Ve-cadherin pathway

Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies

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