Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 302 - 302

Published: Feb. 28, 2025

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility oxidative stress, which contributes neurodegenerative conditions. Alcohol metabolism in brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess metabolized generates reactive oxygen/nitrogen species (ROS/RNS), leading cell injury altering many different Elevated stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction ER death. The literature highlights that alcohol-induced disrupts autophagy mitophagy, contributing neuronal damage. Key mechanisms include dysfunction, epigenetics, accumulation of oxidatively modified proteins, lead neuroinflammation impaired cellular quality control. These processes are exacerbated chronic exposure, resulting suppression protective pathways like NRF2-mediated antioxidant responses increased changes brain. Alcohol-mediated neurotoxicity involves complex interactions between metabolism, regulation, influenced various factors such as drinking patterns, nutritional status, genetic/environmental factors, highlighting need for molecular studies unravel these develop targeted interventions.

Language: Английский

---

Animal models of acute liver failure

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 67 - 77

Published: Jan. 1, 2025

Language: Английский

---

Unravelling the Role of PANoptosis in Liver Diseases: Mechanisms and Therapeutic Implications

Liver International, Journal Year: 2025, Volume and Issue: 45(4)

Published: March 21, 2025

PANoptosis is a multimodal form of cell death that involves inflammatory, apoptotic, and necroptotic pathways, playing key role in the development liver diseases. This article first outlines definition characteristics PANoptosis, then explores its mechanisms action different types diseases, including acute injury, failure, metabolic dysfunction-associated fatty disease, hepatocellular carcinoma. Furthermore, this analyses molecular regulatory network potential therapeutic targets. Finally, summarises current research on diseases future directions, it reviews emerging mechanism

Language: Английский

---

Utilizing Nanoparticles of Hesperidin Loaded on Layered Double Hydroxide to Reduce Hepatotoxicity Caused by Paracetamol in Rats: Controlling of Biotransformation, Oxidative Stress, Inflammation, and Apoptosis

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 429 - 429

Published: March 27, 2025

Background/Objectives: The most used antipyretic and pain relief treatment is paracetamol (acetaminophen), also known as N-acetyl-para-aminophenol (APAP). However, it considered potentially hazardous if consumed repeatedly in large doses or over prolonged periods. This investigation explores the effectiveness of hesperidin (Hesp) Hesp loaded on layered double hydroxide nanoparticles (Hesp-NPs) inhibiting progression acute hepatotoxicity rats induced by APAP. Methods: LDH-Hesp-NPs were prepared characterized. Male Wistar orally treated with Hesp-NPs at same adjusted dose (100 mg/kg) every other day for six weeks. After 2 h first Hesp-NPs, received one oral APAP (750 mg/kg). Results: Administering to APAP-treated significantly reduced oxidant parameter (malondialdehyde) serum enzymes (ALT, AST, LDH, ALP) associated liver function. Antioxidant markers liver, such catalase glutathione, increased notably. Moreover, enhanced mRNA expression UGT1A6, IL-10, HO-1. Conversely, expressions CYP1A1, KEAP1, TGF-β, P53, BAX decreased. These improvements biochemical molecular corroborated histopathology. Conclusions: protect against APAP-induced male rats. was more potent. protective effects may be mediated via modulation biotransformation, oxidative stress, inflammation apoptosis.

Language: Английский

---

The role of Triglyceride Glucose-Waist Circumference (TyG_WC) in predicting metabolic dysfunction-associated steatotic liver disease among individuals with hyperuricemia

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 4, 2025

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with hyperuricemia is significantly high. aim this study was to identify effective biomarkers for the detection MASLD patients hyperuricemia. We conducted an analysis involving 3424 participants from National Health and Nutrition Examination Survey (1999-2020). To potential significant variables, we employed Boruta's algorithm, SHapley Additive exPlanations (SHAP) random forests. Multivariable logistic regression models were utilized assess odds ratio (OR) developing MASLD. evaluate accuracy clinical value our prediction model, receiver operating characteristic (ROC) curves decision curve (DCA) curves. Among population (mean [SD] age, 54 [20] years, 1788 [52.22%] males) hyperuricemia, 1670 had Using SHAP forests, suggested that Triglyceride Glucose-Waist Circumference (TyG_WC) one most variables in predicting risk, area under (AUROC) 0.865. restricted spline (RCS) revealed a positive association between TyG_WC MASLD, when compared lowest quantile TyG_WC, risk highest 137.96 times higher. predictive strategy incorporating notably enhanced threshold probabilities spanning approximately 0% 100%, resulting improvement net benefit. Our found

Language: Английский

---

Investigating Oxidative Stress and Histopathological Changes in The Liver of Hyperglycemic Rats

Balıkesır Health Sciences Journal, Journal Year: 2025, Volume and Issue: 14(1), P. 101 - 106

Published: March 28, 2025

Objective: This study aimed to investigate the impact of hyperglycemia on liver in rats. Materials and Methods: An experimental diabetes was created by intraperitoneal streptozotocin administration Sprague-Dawley rats, blood glucose levels over 250 dl/kg were counted as diabetic. The experiment continued for 6 weeks, weight observed weekly. After sacrification, tissues fixed with formaldehyde enclosed paraffin histological analysis. Hematoxylin eosin staining carried out 4 µm sections taken from blocks, evaluated histopathologically. At same time, apoptosis examined immunohistochemically those active caspase-3 labeling. Finally, oxidative stress status tissue analyzed hydrogen peroxide (H2O2) superoxide dismutase (SOD) levels. Results: results revealed a significant elevation H2O2 slight decline SOD group. Additionally, apoptotic hepatocyte numbers elevated. Histopathological analysis disrupted lobular structure, dilatation central vein sinusoids, shrinkage, lymphocytic infiltration Conclusion: underscores critical role dysfunction caused diabetes, highlighting need novel therapeutic strategies protect against hyperglycemia-induced damage improve outcomes diabetic patients.

Language: Английский

---

Seeds-and-Soil Inspired Hydrogel Microspheres: A Dual-Action Antioxidant and Cellular Therapy for Reversing Intervertebral Disc Degeneration

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123326 - 123326

Published: April 1, 2025

Language: Английский

---

Identification of Mitophagy-Associated Genes for the Prediction of Metabolic Dysfunction-Associated Steatohepatitis Based on Interpretable Machine Learning Models

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 2711 - 2730

Published: May 1, 2024

Background: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes diagnostic models with potential. Methods: The gene expression profiles clinical information MASH patients healthy controls were obtained from Gene Expression Omnibus database (GEO). Limma functional enrichment analysis used identify differentially expressed (mito-DEGs) patients. Machine learning select mito-DEGs evaluate their efficacy early diagnosis MASH. levels validated using datasets cell models. A nomogram was constructed assess risk progression based on mito-DEGs. molecular subtypes evaluated. Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, TIGAR identified. Among machine employed, Support Vector demonstrated highest AUC value 0.935, while Light Gradient Boosting model exhibited accuracy (0.9189), kappa (0.7204), F1-score (0.9508) values. Based these models, RETREG1 selected for further analysis. logistic regression could accurately predict diagnosis. DEGs excellent prediction performance. three independent results found be consistent findings through bioinformatics Furthermore, our revealed significant differences patterns, immune characteristics, biological functions, pathways between Subtype-specific small-molecule drugs identified CMap database. Conclusion: Our research provides novel insights into mitophagy uncovers targets predictive personalized treatments. Keywords: steatohepatitis, mitophagy, biomarkers, model,

Language: Английский

---

Recent developments in the design of functional derivatives of edaravone and exploration of their antioxidant activities

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Language: Английский

---

Melatonin Prevents Thioacetamide–Induced Gut Leakiness and Liver Fibrosis Through the Gut–Liver Axis via Modulating Sirt1‐Related Deacetylation of Gut Junctional Complex and Hepatic Proteins

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(6)

Published: Sept. 1, 2024

ABSTRACT Intestinal barrier dysfunction with high serum endotoxin is common in patients liver fibrosis, but the mechanisms underlying fibrosis remain unclear. Melatonin a well‐recognized antioxidant and an anti‐inflammatory agent that benefits multiple organs. However, beneficial effects of melatonin on gut leakiness–associated have not been systemically studied. Here, we investigated protective against thioacetamide (TAA)–induced hepatic by focusing posttranslational protein modifications through gut–liver axis. Our results showed leakiness markers, including decreased tight/adherens junction proteins (TJ/AJs) increased intestinal deformation, apoptosis, endotoxin, were observed early at 1 week after TAA exposure. Liver injury, prominent 2 4 weeks. Mechanistically, found TJ/AJs hyper‐acetylated, followed ubiquitin‐dependent proteolysis, leading to their degradation leakiness. Gut dysbiosis, hyper‐acetylation, SIRT1 downregulation also observed. Consistently, Sirt1 deficiency greatly enhanced leakiness, endotoxemia, fibrosis. Pretreatment prevented or improved all these changes both liver. Furthermore, blunted acetylation injury TAA–exposed T84 human AML12 mouse cells. Overall, this study demonstrated novel which prevents axis attenuating proteins. Thus, consumption can become potentially safe supplement for preventing hyper‐acetylation

Language: Английский

---