Role of cytochrome P450s in the generation and metabolism of reactive oxygen species

Current Opinion in Toxicology, Journal Year: 2017, Volume and Issue: 7, P. 44 - 51

Published: Oct. 13, 2017

Language: Английский

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Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates

Chemical Research in Toxicology, Journal Year: 2016, Volume and Issue: 29(12), P. 1936 - 1955

Published: Sept. 23, 2016

The liver is an organ with critical importance for drug treatment as the disposition and response to a given often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility drug-induced injury, which constitutes major risk development programs causing attrition of promising candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies 2D hepatocyte systems have been used examination human metabolism toxicity. Yet, these models are far from satisfactory due extensive species differences because hepatocytes cultures rapidly dedifferentiate resulting loss their phenotype functionality. With increasing comprehension that 3D cell culture more accurately reflect vivo physiology, recent decade research has focused on optimization various strategies attempt preserve properties vitro. In this contribution, we critically review developments, resulted arsenal different static perfused models. These include sandwich-cultured hepatocytes, spheroid platforms, microfluidic multiorgan biochips. Importantly, many maintain prolonged times, allows probing potential newly developed chemical entities cause chronic hepatotoxicity. Moreover, some platforms permit investigation action specific genetic backgrounds diseased thereby significantly expanding repertoire tools detect injuries. It concluded hitherto fruitful now at hand whose sensitivity specificity detecting hepatotoxicity superior those classical systems. For future, highlight need develop integrated coculture model emulate immunotoxicities arise complex interactions between immune cells.

Language: Английский

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MicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages

Journal of Biological Chemistry, Journal Year: 2015, Volume and Issue: 291(1), P. 149 - 159

Published: Nov. 3, 2015

Language: Английский

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Pathophysiological Aspects of Alcohol Metabolism in the Liver

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5717 - 5717

Published: May 27, 2021

Alcoholic liver disease (ALD) is a globally prevalent chronic caused by or binge consumption of alcohol. The the major organ that metabolizes alcohol; therefore, it particularly sensitive to alcohol intake. Metabolites and byproducts generated during metabolism cause damage, leading ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, inducing fibrosis. Despite severity ALD, development novel treatments has been hampered lack animal models fully mimic human ALD. To overcome current limitations studies therapy development, necessary understand molecular mechanisms underlying alcohol-induced injury. Hence, provide insights into progression this review examines previous conducted on in liver. There particular focus occurrence hepatotoxicity originating from metabolism.

Language: Английский

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EGFR Signaling in Liver Diseases

International Journal of Molecular Sciences, Journal Year: 2015, Volume and Issue: 17(1), P. 30 - 30

Published: Dec. 29, 2015

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. EGFR axis has been shown play key role during liver regeneration following acute chronic damage, as well in cirrhosis hepatocellular carcinoma (HCC) highlighting importance development diseases. Despite frequent overexpression human HCC, clinical studies with inhibitors have so far only modest results. Interestingly, recent study HCC mouse models upregulated macrophages where it plays tumor-promoting function. Thus, diseases appears be more complex than what anticipated. Further are needed improve molecular understanding cell-specific control disease progression able develop better therapies targeting major components network selected cell types. In this review, we compiled current knowledge different damage diseases, derived from analysis lines genetically engineered (GEMMs).

Language: Английский

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An Observational Data Meta-analysis on the Differences in Prevalence and Risk Factors Between MAFLD vs NAFLD

Clinical Gastroenterology and Hepatology, Journal Year: 2021, Volume and Issue: 21(3), P. 619 - 629.e7

Published: Dec. 4, 2021

Language: Английский

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Alcohol Use in Patients with Chronic Liver Disease

New England Journal of Medicine, Journal Year: 2018, Volume and Issue: 379(13), P. 1251 - 1261

Published: Sept. 26, 2018

Alcohol use is common in patients with liver disease, but medications effective alcohol-use disorder are used sparingly. Even advanced disease should receive treatment for disorder.

Language: Английский

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Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study

Hepatology, Journal Year: 2017, Volume and Issue: 66(5), P. 1464 - 1473

Published: May 1, 2017

Understanding the mechanisms of outcome according to time frame can help optimize therapeutic development in severe alcoholic hepatitis. We assessed short-term and long-term survival hepatitis based on baseline disease severity, extent improvement, influence alcohol relapse, their interaction. Data consumption were prospectively recorded 398 patients treated with corticosteroids short term (from corticosteroid initiation 6 months) long months maximum follow-up time). Cumulative incidence rate first relapse was 25.2%, 33.7%, 35.2% at 1, 3, 5 years, respectively. Alcohol (≥30 g/day) not associated mortality (P = 0.24) during period (1,606 patient-months risk), but Lille < 0.0001) Model for End-Stage Liver Disease scores independent prognostic factors. In who alive (median follow-up, 42 months; interquartile range 11-88), corresponding 10,413 risk, (hazard ratio, 3.9; P 0.0001). Additional analysis abstinent as a reference showed dose effect hazard ratio death: 2.36 0.052) 1-29 g/day, 3.2 0.003) 30-49 3.51 50-99 5.61 ≥ 100 g/day. The score predictive outcome, while 0.02) factors.This study shows that new must target liver injury term; thus, health agencies endorse future designs adapted factors influencing mortality; this mind, drug-targeting involved should only be tested period. (Hepatology 2017;66:1464-1473).

Language: Английский

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Roseburia spp. Abundance Associates with Alcohol Consumption in Humans and Its Administration Ameliorates Alcoholic Fatty Liver in Mice

Cell Host & Microbe, Journal Year: 2019, Volume and Issue: 27(1), P. 25 - 40.e6

Published: Dec. 19, 2019

Language: Английский

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The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis hepatocellular carcinoma, is serious health problem worldwide. In recent years, many natural foods herbs with abundant phytochemicals have been proposed as supplementation for patients hepatic disorders. As an important category phytochemicals, polyphenols attracted increasing attention potential agents the prevention treatment diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, inflammation put spotlight therapies It has reported that exert therapeutic effects on injuries via complicated mechanisms. Therefore, it necessary systematical review sort out current researches help better understand potentials this review, we aim summarize update existing evidence various diseases by vitro , vivo clinical studies, while special paid action

Language: Английский

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