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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Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle

Pharmacology & Therapeutics, Год журнала: 2021, Номер 231, С. 107988 - 107988

Опубликована: Сен. 16, 2021

Язык: Английский

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The Influence of Gut Dysbiosis in the Pathogenesis and Management of Ischemic Stroke

Cells, Год журнала: 2022, Номер 11(7), С. 1239 - 1239

Опубликована: Апрель 6, 2022

Recent research on the gut microbiome has revealed influence of microbiota (GM) ischemic stroke pathogenesis and treatment outcomes. Alterations in diversity, abundance, functions microbiome, termed dysbiosis, results dysregulated gut–brain signaling, which induces intestinal barrier changes, endotoxemia, systemic inflammation, infection, affecting post-stroke Gut–brain interactions are bidirectional, signals from to brain mediated by microbially derived metabolites, such as trimethylamine N-oxide (TMAO) short-chain fatty acids (SCFAs); bacterial components, lipopolysaccharide (LPS); immune cells, T helper cells; translocation via hormonal, immune, neural pathways. Ischemic affects microbial composition hypothalamic–pituitary–adrenal (HPA) pathways, can contribute Experimental clinical studies have demonstrated that restoration usually improves outcomes regulating metabolic, inflammatory responses axis (GBA). Therefore, restoring healthy ecology may be a key therapeutic target for effective management stroke.

Язык: Английский

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Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review

Cells, Год журнала: 2022, Номер 11(8), С. 1362 - 1362

Опубликована: Апрель 16, 2022

Depression is a highly common mental disorder, which often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated clear correlation between gut dysbiosis (GD) or microbial and the development of anxiety depressive behaviors. The microbiome communicates brain through neural, immune, metabolic pathways, either directly (via vagal nerves) indirectly gut- microbial-derived metabolites as well hormones endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, ghrelin). Maintaining healthy microbiota (GM) now being recognized important for health use probiotics, prebiotics, synbiotics, fecal transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM hypothalamus–pituitary–adrenal (HPA) axis functions. In this review, we summarized etiopathogenic link depression preclinical clinical evidence. addition, collated information on recent therapies supplements, such short-chain fatty acids, vitamin B12, omega-3 etc., target gut–brain (GBA) effective management behavior anxiety.

Язык: Английский

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Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Язык: Английский

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Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3148 - 3148

Опубликована: Март 28, 2025

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development progression of chronic diseases. This review provides comprehensive analysis complex interplay between these two factors, focusing on how an imbalance reactive oxygen species (ROS) antioxidants leads to OS, disrupting cellular homeostasis contributing range conditions, including metabolic disorders, cardiovascular diseases, neurological cancer. The microbiota, diverse community microorganisms residing gastrointestinal tract, is essential for regulating immune responses, pathways, overall health. Dysbiosis, composition, closely associated with inflammation, dysfunction, various highlights influences influenced by complicating pathophysiology many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators crosstalk OS microbiota. EVs also play signaling host tissues, modulating processes. function holds promise targeted therapies aimed at restoring microbial balance mitigating OS. Personalized therapeutic approaches, probiotics, antioxidants, fecal transplantation-based strategies, can be used address OS-related diseases improve health outcomes. Nonetheless, further research needed study molecular mechanisms underlying interactions potential innovative interventions offer novel strategies managing enhancing

Язык: Английский

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Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Март 8, 2022

Background Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective safe means to alleviate these complications. Purpose We aimed assess the oral-gut microbiota profiles THW then investigate whether probiotics could alleviating related therapeutic effects were associated with state. Methods Fifty eligible carcinoma undergoing thyroidectomy randomly assigned receive or placebo during THW. Complications assessed through validated questionnaires plasma lipid indicators. The complex preparation was composed of Bifidobacterium infantis , Lactobacillus acidophilus Enterococcus faecalis Bacillus cereus . Results Probiotics alleviated lack energy, constipation, weight gain, dry mouth decreased levels fecal/serum LPS indicators (total cholesterol, triglycerides, low-density lipoprotein, apolipoprotein A) (P < 0.05). Gut oral microbial diversity significantly after THW, while an increased dysbiosis index (MDI) observed. distinctly restored gut diversity. Increased Holdemanella Coprococcus_2 Fusobacterium Eubacterium_ruminantium_group Ruminococcus_1 Parasutterella found intervention. Lack seen be above microbiota. In addition, reduced Prevotella_9 Haemophilus Lautropia which positively correlated occurrence mouth. Conclusion reduce incidence may modifying Clinical Trial Registration [ https://clinicaltrials.gov/ ], identifier America Registry NCT03574051.

Язык: Английский

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ALDH2 deficiency increases susceptibility to binge alcohol-induced gut leakiness, endotoxemia, and acute liver injury in mice through the gut-liver axis

Redox Biology, Год журнала: 2022, Номер 59, С. 102577 - 102577

Опубликована: Дек. 13, 2022

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme responsible for metabolizing toxic acetaldehyde to acetate and acts as a protective or defensive protein against various disease states associated with alcohol use disorder (AUD), including alcohol-related liver (ARLD). We hypothesized that Aldh2-knockout (KO) mice are more susceptible binge alcohol-mediated injury than wild-type (WT) through increased oxidative stress, gut leakiness endotoxemia. Therefore, this study aimed investigate role of ALDH2 in alcohol-induced permeability, endotoxemia, acute inflammatory by exposing Aldh2-KO WT single oral dose 3.5, 4.0, 5.0 g/kg. Our findings showed first time deficiency increases their sensitivity nitrative enterocyte apoptosis, nitration tight junction (TJ) adherent (AJ) proteins, leading degradation. These resulted endotoxemia after exposure ethanol even at 3.5 g/kg, while no changes were observed corresponding mice. The elevated serum endotoxin (lipopolysaccharide, LPS) bacterial translocation contributed systemic inflammation, hepatocyte subsequently gut-liver axis. Treatment Daidzin, an inhibitor, exacerbated ethanol-induced cell permeability reduced TJ/AJ proteins T84 human colon cells. reversed Alda-1, activator. Furthermore, CRISPR/Cas9-mediated knockout cells damage paracellular permeability. All these demonstrate critical epithelial barrier dysfunction suggest gene mutation humans risk factor injury, could be important therapeutic target alcohol-associated tissue organ damage.

Язык: Английский

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Antioxidant Materials in Oral and Maxillofacial Tissue Regeneration: A Narrative Review of the Literature

Antioxidants, Год журнала: 2023, Номер 12(3), С. 594 - 594

Опубликована: Фев. 27, 2023

Oral and maxillofacial tissue defects caused by trauma, tumor reactions, congenital anomalies, ischemic diseases, infectious surgical resection, odontogenic cysts present a formidable challenge for reconstruction. Tissue regeneration using functional biomaterials cell therapy strategies has raised great concerns in the treatment of damaged during past few decades. However, implantation transplantation, production excessive reactive oxygen species (ROS) may hinder repair as it commonly causes severe injuries leading to damage. These products exist form oxidant molecules such hydrogen peroxide, superoxide ions, hydroxyl radicals, nitrogen oxide. days, many scientists have focused on application ROS-scavenging components body process. One these scavenging is antioxidants, which are beneficial materials tissues keeping safe against free radicals. Antioxidants divided into natural synthetic sources. In current review article, different antioxidant sources their mechanism action discussed. The applications antioxidants oral tissues, including hard cranial, alveolar bone, dental tissue, soft (dental pulp, periodontal tissue), facial nerve, cartilage also highlighted following parts.

Язык: Английский

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Role of the gut microbiota in complications after ischemic stroke

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Апрель 5, 2024

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction communication between the intestines brain. Recent studies have reported alterations gut microbiota diversity post-IS, suggesting involvement of post-IS complications through various mechanisms bacterial translocation, immune regulation, production metabolites, thereby affecting disease prognosis. In this review, to provide insights into prevention treatment improvement long-term prognosis IS, we summarize interaction along with effects on complications.

Язык: Английский

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