Hepatic co-cultures in vitro reveal suitable to detect Nrf2-mediated oxidative stress responses on the bladder carcinogen o -anisidine

Wewering, Franziska; Jouy, Florent; Caliskan, Sükran; Kalkhof, Stefan; Bergen, Martin von; Luch, Andreas; Zellmer, Sebastian

doi:10.1016/j.tiv.2017.01.006

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…In order to avoid the scarcity of fresh tissue to isolate both PHHs and NPCs, such as KCs, some authors have used alternative cell sources, such as HepG2 and THP-1 monocytes/macrophages, for co-culturing purposes [ 83 , 146 ]. The co-cultures of HepG2 cells and THP-1 macrophages showed increased toxicity to troglitazone, trovafloxacin, diclofenac and ketoconazole in the presence of TNF-α or LPS, confirming that an inflammatory microenvironment enhances the sensitivity of liver cells towards iDILI drugs [ 83 ].…”

Section: In Vitro Cell Models For Chronic Hepatotoxicitymentioning

confidence: 99%

In Vitro Models for Studying Chronic Drug-Induced Liver Injury

Donato

Ferrer

Tolosa

2022

IJMS

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Drug-induced liver injury (DILI) is a major clinical problem in terms of patient morbidity and mortality, cost to healthcare systems and failure of the development of new drugs. The need for consistent safety strategies capable of identifying a potential toxicity risk early in the drug discovery pipeline is key. Human DILI is poorly predicted in animals, probably due to the well-known interspecies differences in drug metabolism, pharmacokinetics, and toxicity targets. For this reason, distinct cellular models from primary human hepatocytes or hepatoma cell lines cultured as 2D monolayers to emerging 3D culture systems or the use of multi-cellular systems have been proposed for hepatotoxicity studies. In order to mimic long-term hepatotoxicity in vitro, cell models, which maintain hepatic phenotype for a suitably long period, should be used. On the other hand, repeated-dose administration is a more relevant scenario for therapeutics, providing information not only about toxicity, but also about cumulative effects and/or delayed responses. In this review, we evaluate the existing cell models for DILI prediction focusing on chronic hepatotoxicity, highlighting how better characterization and mechanistic studies could lead to advance DILI prediction.

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Section: In Vitro Cell Models For Chronic Hepatotoxicitymentioning

confidence: 99%

In Vitro Models for Studying Chronic Drug-Induced Liver Injury

Donato

Ferrer

Tolosa

2022

IJMS

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“…Noticeable rise in ROS production, because of excessive glucocorticoids secretion during prolonged stress, activates liver degenerative processes through extrinsic and intrinsic pathways of cell death. Alongside these detrimental effects of the glucocorticoids, “The Kelch ECH associated protein 1 (Keap1) -Nrf2 pathway” which promotes liver regeneration [14, 52] is also activated by the glucocorticoids. Thus, both apoptosis and regenerative pathways are fine-tuned by the glucocorticoids signaling and the outcome would be determined by alteration in any of the two mechanisms.…”

Section: The Impact Of Psychosocial Stress and Glucocorticoids On Bodmentioning

confidence: 99%

“…It was shown that Nrf2/antioxidant response element (ARE) system is an effective way to control ALR expression necessary for hepatic regeneration [20]. Another study showed that ROS-induced Nrf2 is capable of triggering transcription of proteins that play vital role in cell redox homeostasis function [52]. Taken together, these studies provide evidence that the stress factors or mediators play an important role in the regulation of liver regeneration pathways.…”

Section: Pathways Linking Psychosocial Stress To Liver Regenerationmentioning

confidence: 99%

Psychosocial-Stress, Liver Regeneration and Weight Gain: a Conspicuous Pathophysiological Triad

Ishtiaq

Khan

Arshad

2018

Cell Physiol Biochem

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Psychosocial stress alters several physiological parameters resulting in multiple disorders, particularly compromising the immune system thereby provoking various diseases including liver disorders. However, the plausible underlying mechanisms remain elusive. Recent literature provides mechanistic evidences of detrimental effects of psychosocial stress on physiology of different body organs including liver. The data of stress-induced pathophysiological changes in liver functions and obesity were systematically collected from PubMed, ScienceDirect and the Web of Science Databases published in English. Stress and glucocorticoids (GCs) control food intake and energy expenditure through appetite stimulators neuropeptide Y (NYP) and agouti-related protein (AgRP) in hypothalamus. Principle effectors of the activated hypothalamic-pituitary-adrenal (HPA) axis in response to psychosocial stress are proopiomelanocortin (POMC)-derived adrenocorticotropic hormone (ACTH) and GCs. Stress-induced GCs hyper-secretion triggers glucocorticoid receptor (GR)-dependent transcriptional factor, nuclear factor kappa B (NFκB), which interferes TNFα-IL6 and keap1-Nrf2 pathways in liver regeneration and obesity through fine-tuning of TNFα, IL6 and Nrf2 signaling. In this review, it is contrived upon existing evidence to put forward a model whereby exposure to life-stress has a prominent impact over weight gain and can alter the regenerative mode of a damaged liver through Keap1-Nrf2 and TNFa-IL6 pathways.

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