scholarly journals Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 165 ◽  
Author(s):  
Ondřej Brózman ◽  
Barbara Kubickova ◽  
Pavel Babica ◽  
Petra Laboha
Keyword(s):  
Human Health ◽  
Respiratory System ◽  
Intracellular Signaling ◽  
Liver Toxicity ◽  
Organic Anion ◽  
In Vitro Models ◽  
Cyanobacterial Blooms ◽  
Bronchial Epithelial ◽  
Mitogen Activated Protein

Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 μM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.

scholarly journals In vitro models for liver toxicity testing

2013 ◽  
Vol 2 (1) ◽  
pp. 23-39 ◽  
Author(s):  
Valerie Y. Soldatow ◽  
Edward L. LeCluyse ◽  
Linda G. Griffith ◽  
Ivan Rusyn
Keyword(s):  
Liver Toxicity ◽  
Toxicity Testing ◽  
In Vitro Models

scholarly journals Activation of MAPKs in human bronchial epithelial cells exposed to metals

1998 ◽  
Vol 275 (3) ◽  
pp. L551-L558 ◽  
Author(s):  
James M. Samet ◽  
Lee M. Graves ◽  
Jacqueline Quay ◽  
Lisa A. Dailey ◽  
Robert B. Devlin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Subsequent Increase ◽  
Induced Expression ◽  
Bronchial Epithelial ◽  
Mitogen Activated Protein ◽  
Metallic Compounds ◽  
Factor Α

We have previously shown that in vitro exposure to metallic compounds enhances expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-α in human bronchial epithelial cells. To characterize signaling pathways involved in metal-induced expression of inflammatory mediators and to identify metals that activate them, we studied the effects of As, Cr, Cu, Fe, Ni, V, and Zn on the mitogen-activated protein kinases (MAPK) extracellular receptor kinase (ERK), c-Jun NH2-terminal kinase (JNK), and P38 in BEAS cells. Noncytotoxic concentrations of As, V, and Zn induced a rapid phosphorylation of MAPK in BEAS cells. Activity assays confirmed marked activation of ERK, JNK, and P38 in BEAS cells exposed to As, V, and Zn. Cr and Cu exposure resulted in a relatively small activation of MAPK, whereas Fe and Ni did not activate MAPK under these conditions. Similarly, the transcription factors c-Jun and ATF-2, substrates of JNK and P38, respectively, were markedly phosphorylated in BEAS cells treated with As, Cr, Cu, V, and Zn. The same acute exposure to As, V, or Zn that activated MAPK was sufficient to induce a subsequent increase in IL-8 protein expression in BEAS cells. These data suggest that MAPK may mediate metal-induced expression of inflammatory proteins in human bronchial epithelial cells.

Chemical-based risk assessment and in vitro models of human health effects induced by organic pollutants in soils from the Olona valley

2013 ◽  
Vol 463-464 ◽  
pp. 790-801 ◽  
Author(s):  
Diego Baderna ◽  
Andrea Colombo ◽  
Giorgia Amodei ◽  
Stefano Cantù ◽  
Federico Teoldi ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Human Health ◽  
Health Effects ◽  
Organic Pollutants ◽  
In Vitro Models ◽  
Human Health Effects

In Vitro Models of Liver Toxicity

1996 ◽  
pp. 99-117
Author(s):  
R. G. Thurman ◽  
P. E. Ganey ◽  
S. A. Belinsky ◽  
J. G. Conway ◽  
M. Z. Badr
Keyword(s):  
Liver Toxicity ◽  
In Vitro Models

scholarly journals Activation of mitogen-activated protein kinases by a splice variant of GHRH receptor

2009 ◽  
Vol 44 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Nektarios Barabutis ◽  
Agnieszka Siejka ◽  
Andrew V Schally ◽  
Norman L Block ◽  
Renzhi Cai ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Protein Kinases ◽  
Mechanism Of Action ◽  
Intracellular Signaling ◽  
Splice Variants ◽  
Nuclear Antigen ◽  
Proliferative Cell Nuclear Antigen ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Hypothalamic GHRH controls the release of GH from the pituitary gland and also acts as a growth factor in a variety of cancers. The mitogenetic activity of GHRH is exerted through the binding to the pituitary type receptor (pGHRH-R) and its splice variants, mainly SV1. The intracellular signaling pathways that are activated upon the binding of GHRH to the SV1 receptor have not been elucidated. HeLa cervical cancer cells do not express GHRH or GHRH receptors (GHRHRs) and thus do not respond to GHRH or GHRH antagonists. In order to elucidate the mechanism of action of SV1 receptor, we transfected HeLa cells with plasmids for pcDNA3-GHRHR or pcDNA3-SV1. The transfected cells responded to both GHRH (1–29)NH2 and GHRH antagonist MZ-5-156, as shown by an increase or decrease respectively in the proliferation rate in vitro and the expression of proliferative cell nuclear antigen. We also demonstrated that when the cells transfected with SV1 plasmid are stimulated with GHRH (1–29)NH2, SV1 receptor activates the mitogen-activated protein kinases pathway (MAPKs), as shown previously for the cells that express pGHRH-R. Our results show, for the first time, the activation of the MAPKs cascade by the SV1 receptor. Since SV1 receptor is found in various tumors and mediates the responses to GHRH and synthetic antagonists, our findings shed light on the mechanism of action of SV1 receptor in cancer cells.

scholarly journals Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofin-vitroliver technologies

TECHNOLOGY ◽  
2015 ◽  
Vol 03 (01) ◽  
pp. 1-26 ◽  
Author(s):  
O. B. Usta ◽  
W. J. McCarty ◽  
S. Bale ◽  
M. Hegde ◽  
R. Jindal ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Focal Point ◽  
Large Body ◽  
In Vitro Models ◽  
The Body ◽  
Characterization Methods ◽  
Cellular Environment ◽  
Tissue Systems

The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism's toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop "organs-on-a-chip". One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.

scholarly journals Testing different concentrations of both hydrocortisone and rifampicin toward pregnane X receptor activation suggest their protective effect against liver toxicity.

2019 ◽  
Author(s):  
Elham Alshammari
Keyword(s):  
Protective Effect ◽  
Clinical Setting ◽  
Graft Failure ◽  
Liver Toxicity ◽  
Luciferase Activity ◽  
Pregnane X Receptor ◽  
Receptor Activation ◽  
In Vitro Models ◽  
Liver Inflammation

In different animal and human (in vitro) models, PXR activation resulted in suppressed liver inflammation and fibrosis which in return suggest graft survival. In this study, different concentrations of hydrocortisone (HC) and rifampicin were tested for PXR activity. For each drug, transfected HEPG2 cells were treated with different molar concentrations and then luciferase activity for both firefly and renilla were recorded. Both hydrocortisone and rifampicin produced an increase in PXR activity. Correlation between PXR activation and graft failure must be addressed in clinical setting.

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