A synopsis on aging—Theories, mechanisms and future prospects

Ageing Research Reviews, Год журнала: 2016, Номер 29, С. 90 - 112

Опубликована: Июнь 26, 2016

Язык: Английский

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Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Cells, Год журнала: 2019, Номер 9(1), С. 24 - 24

Опубликована: Дек. 20, 2019

Liver fibrosis is a regenerative process that occurs after injury. It characterized by the deposition of connective tissue specialized fibroblasts and concomitant proliferative responses. Chronic damage stimulates fibrogenic processes in long-term may result excess matrix impairment liver functions. End-stage referred to as cirrhosis predisposes strongly loss functions (decompensation) hepatocellular carcinoma. pathology common number different chronic diseases, including alcoholic disease, non-alcoholic fatty viral hepatitis. The predominant cell type responsible for fibrogenesis hepatic stellate cells (HSCs). In response inflammatory stimuli or hepatocyte death, HSCs undergo trans-differentiation myofibroblast-like cells. Recent evidence shows metabolic alterations are important thus offer new possibilities therapeutic interventions. aim this review summarize current knowledge changes occur during HSC activation with particular focus on retinol lipid metabolism, central carbon associated redox stress-related signaling pathways.

Язык: Английский

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CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 8221 - 8221

Опубликована: Июль 30, 2021

CYP2E1 is one of the fifty-seven cytochrome P450 genes in human genome and highly conserved. a unique enzyme because its heme iron constitutively high spin state, allowing direct reduction of, e.g., dioxygen, causing formation variety reactive oxygen species xenobiotics to toxic products. The has been focus scientific interest due (i) important endogenous function liver homeostasis, (ii) ability activate procarcinogens convert certain drugs, paracetamol anesthetics, cytotoxic end products, (iii) effectively reduce dioxygen radical injury, (iv) capability compounds, often generating intermediates or indirect immunotoxic properties (v) contribution development alcoholic disease, steatosis NASH. In this overview, we present discovery studies humans, 3D systems genetically modified mice disclose clinical relevance. Induction either by alcohol high-fat diet leads increased severity pathology likelihood develop ALD NASH, with subsequent influence on occurrence hepatocellular cancer. Thus, fat-dependent induction might provide link between fibrosis liver. We conclude that many physiological functions key for hepatic carcinogenesis, drug toxicity disease.

Язык: Английский

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Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression

Journal of Hepatology, Год журнала: 2016, Номер 66(3), С. 601 - 609

Опубликована: Ноя. 18, 2016

Язык: Английский

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Oxidative stress in alcohol-related liver disease

World Journal of Hepatology, Год журнала: 2020, Номер 12(7), С. 332 - 349

Опубликована: Июль 23, 2020

Alcohol consumption is one of the leading causes global burden disease and results in high healthcare economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which responsible for a significant proportion alcohol-attributable deaths globally. Other than reducing consumption, there are currently no effective treatments disease. Oxidative stress refers an imbalance production elimination reactive oxygen species antioxidants. It plays important roles several aspects pathogenesis. Here, we review how chronic use oxidative through increased metabolism via cytochrome P450 2E1 system producing species, acetaldehyde protein DNA adducts. These trigger inflammatory signaling pathways within expression pro-inflammatory mediators causing hepatocyte apoptosis necrosis. Reactive exposure also mitochondrial hepatocytes structural functional dysregulation mitochondria upregulating apoptotic signaling. There evidence that as well direct effect influences epigenetic regulation. Increased histone methylation acetylation specific inhibits antioxidant responses promotes key genes. This highlights role pathogenesis warrant further study including Improved understanding these processes may identify novel targets therapy.

Язык: Английский

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Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

Journal of Clinical and Translational Research, Год журнала: 2017, Номер unknown

Опубликована: Янв. 1, 2017

Background: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including liver, steatohepatitis (NASH) and cirrhosis.Different investigations showed or suggested that obesity NAFLD are able increase the risk hepatotoxicity different drugs.Some these drugs could induce more frequently an acute hepatitis in obese individuals whereas others worsen pre-existing NAFLD.Aim: The main objective present review was collect available information regarding role as factor for drug-induced hepatotoxicity.For this purpose, we performed data-mining analysis using queries injury (or DILI), hepatotoxicity, NAFLD), steatosis obesity.The data from collected articles reported when available, some pathophysiological hypotheses put forward.Relevance patients: Drugs pose potential patients include compounds belonging pharmacological classes such acetaminophen, halothane, methotrexate, rosiglitazone, stavudine tamoxifen.For drugs, experimental rodents confirmed clinical observations unveiled mechanisms explain why pharmaceuticals particularly hepatotoxic NAFLD.Other pentoxifylline, phenobarbital omeprazole might also but required determine whether significant not.Because people take several treatment obesity-related diseases type 2 diabetes, hyperlipidemia coronary heart disease, it urgent identify can cause on background worsening.

Язык: Английский

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Autophagy, Oxidative Stress, and Alcoholic Liver Disease: A Systematic Review and Potential Clinical Applications

Antioxidants, Год журнала: 2023, Номер 12(7), С. 1425 - 1425

Опубликована: Июль 14, 2023

Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic disease (ALD). Autophagy is a regulated dynamic that sequesters damaged excess cytoplasmic organelles lysosomal degradation may counteract harmful effects ROS-induced stress. These include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, iron overload. In diseases, particularly ALD, macroautophagy has been implicated as protective mechanism in hepatocytes, although it does not appear play same role stellate cells. Beyond liver, autophagy also mitigate alcohol on other organs, thereby providing an additional layer protection against ALD. potential further supported studies showing drugs interact with autophagy, such rapamycin, can prevent ALD animal models. systematic review presents comprehensive analysis literature, focusing regulation, involvement organ-organ crosstalk relevant autophagy-targeting therapeutic strategies.

Язык: Английский

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Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

PLoS ONE, Год журнала: 2017, Номер 12(2), С. e0172463 - e0172463

Опубликована: Фев. 22, 2017

Drug- and alcohol-induced liver injury are a leading cause of failure transplantation. Emerging evidence suggests that extracellular vesicles (EVs) source biomarkers because they contain unique proteins reflecting the identity tissue-specific origin EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) binge alcohol, can increase amounts circulating EVs evaluate liver-specific potential for injury. The EVs, isolated from plasma APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics biochemical methods. Liver specific analyzed immunoblots ELISA. total in APAP-treated mice significantly increased dose- time-dependent manner. Proteomic analysis APAP-exposed revealed and/or compared those controls. Additionally, protein following APAP exposure returned basal levels when treated with N-acetylcysteine glutathione. Similar results also observed exposed doses thioacetamide d-galactosamine but not non-hepatotoxic penicillin myotoxic bupivacaine. ethanol elevated alcoholics hepatitis, counterparts. These indicate drug- alcohol-mediated hepatic could serve hepatotoxicity.

Язык: Английский

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Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress

Redox Biology, Год журнала: 2018, Номер 18, С. 266 - 278

Опубликована: Июль 21, 2018

Alcoholic liver disease (ALD) is a major chronic worldwide and can range from simple steatosis, inflammation to fibrosis/cirrhosis possibly through leaky gut systemic endotoxemia. We investigated whether pomegranate (POM) protects against binge alcohol-induced leakiness, endotoxemia, inflammatory damage. After POM pretreatment for 10 days, rats were exposed 3 oral doses of alcohol (5 g/kg/dose) or dextrose (as control) at 12-h intervals. Binge exposure induced with significantly elevated plasma endotoxin fatty by increasing the levels oxidative nitrative stress marker proteins such as ethanol-inducible CYP2E1, inducible nitric oxide synthase, nitrated in small intestine liver. reduced barrier dysfunction, inhibiting proteins. restored intestinal tight junction (TJ) ZO-1, occludin, claudin-1, claundin-3 markedly diminished after alcohol-exposure. In addition, adherent (AJ) (e.g., β-catenin E-cadherin) desmosome plakoglobin along associated protein α-tubulin clearly decreased alcohol-exposed but basal POM-pretreated rats. Immunoprecipitation followed immunoblot analyses revealed that claudin-1 was ubiquitinated rats, whereas these modifications blocked pretreatment. These results showed first time prevent leakiness injury suppressing stress.

Язык: Английский

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Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis

The Journal of Nutritional Biochemistry, Год журнала: 2017, Номер 55, С. 12 - 25

Опубликована: Дек. 10, 2017

Язык: Английский

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