Reactive Oxygen Species and Oxidative Stress in the Pathogenesis of MAFLD

Journal of Clinical and Translational Hepatology, Год журнала: 2022, Номер 10(5), С. 939 - 946

Опубликована: Июль 6, 2022

The pathogenesis of metabolic-associated fatty liver disease (MAFLD) is complex and thought to be dependent on multiple parallel hits a background genetic susceptibility. evidence suggests that MAFLD progression dynamic two-way process relating repetitive bouts metabolic stress inflammation interspersed with endogenous anti-inflammatory reparative responses. In MAFLD, excessive hepatic lipid accumulation causes the production lipotoxins induce mitochondrial dysfunction, endoplasmic reticular stress, over reactive oxygen species (ROS). Models show marked disruption function reduced oxidative capacitance impact cellular processes including mitophagy, phosphorylation, biogenesis. excess, ROS modify insulin innate immune signaling alter expression activity essential enzymes involved in homeostasis. can also cause direct damage intracellular structures causing hepatocyte injury death. select cases, use anti-oxidants scavengers have been shown diminish pro-apoptopic effects acids. Given this link, anti-oxidant pathways target interest, Nrf2 activation showing reduction models MAFLD. Thyroid hormone receptor β (THRβ) agonists nuclear peroxisome proliferation-activated (PPAR) family gained interest reducing lipotoxicity restoring Unfortunately, true interplay between clinical molecular components remain only partly understood. Most recently, multiomics-based strategies are being adopted for hypothesis-free analysis changes Transcriptome profiling maps unique genotype-phenotype associations various single-cell transcriptome-based projects underway, there hope novel physiological insights uncover therapeutic targets.

Язык: Английский

---

An overview of ferroptosis in non-alcoholic fatty liver disease

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 153, С. 113374 - 113374

Опубликована: Июль 11, 2022

Non-alcoholic fatty liver disease (NAFLD) is a public health problem associated with high mortality and morbidity rates worldwide. Presently, its complex pathophysiology still unclear, there no specific drug to reverse NAFLD. Ferroptosis an iron-dependent non-apoptotic form of cell death characterized by the iron-induced accumulation lipid reactive oxygen species (ROS), which damage nucleic acids, proteins, lipids; generate intracellular oxidative stress; ultimately cause death. Emerging evidence indicates that ferroptosis involved in progression NAFLD, although mechanism action NAFLD poorly understood. Herein, we summarize certain diseases, especially pathogenesis discuss potential therapeutic approaches currently used treat This review also highlights further directions for treatment prevention related diseases.

Язык: Английский

---

Role of immune responses in the development of NAFLD-associated liver cancer and prospects for therapeutic modulation

Journal of Hepatology, Год журнала: 2023, Номер 79(2), С. 538 - 551

Опубликована: Март 7, 2023

The liver is the central metabolic organ of body, regulating energy and lipid metabolism, while also having potent immunological functions. Overwhelming capacity via obesity a sedentary lifestyle leads to hepatic accumulation, chronic necro-inflammation, enhanced mitochondrial/endoplasmic reticulum stress development non-alcoholic fatty disease (NAFLD), its more severe form steatohepatitis (NASH). Based on an improved understanding pathophysiological mechanisms, specifically targeting pathways prevent or slow down progression NAFLD cancer will become possible. Genetic/environmental factors are known contribute NASH cancer. complex pathophysiology NAFLD-NASH reflected by environmental factors, particularly gut microbiome products. NAFLD-associated HCC most often occurs in context chronically inflamed cirrhotic liver. Recognition alarmins metabolites derived from microbiota metabolically injured create strong inflammatory milieu supported innate adaptive immunity. Several recent studies indicate that steatosis induces auto-aggressive CD8+CXCR6+PD1+ T cells eliminate parenchymal non-parenchymal antigen-independent manner. This promotes damage pro-tumorigenic environment. possess exhausted, hyperactivated, resident phenotype; they trigger transition might be responsible for weaker responses immune checkpoint inhibitors - particular atezolizumab/bevacizumab. Here, we provide overview NASH-related inflammation/pathogenesis, focusing new discoveries role cells. review discusses preventive measures halt therapeutic strategies manage patients with NASH-HCC.

Язык: Английский

---

Reactive oxygen species-sensitive materials: A promising strategy for regulating inflammation and favoring tissue regeneration

Smart Materials in Medicine, Год журнала: 2023, Номер 4, С. 427 - 446

Опубликована: Янв. 1, 2023

Reactive oxygen species (ROS), acting as essential mediators in the biological system, highly influence physiologic and pathologic processes of human body. The aberrant production ROS, caused by various diseases, may lead to inflammation cellular damages, well homeostasis disruption. In recent years, biomaterials sensitive stimuli have received increasing attention due their potential for achieving more specific diagnoses effective treatments. Particularly, ROS-responsive could be triggered ROS damaged tissue microenvironment release payloads or exert a therapeutically beneficial effect, consequently regulating elevated level downregulating oxidative stress promote regeneration. this review, we outline underlying mechanisms generation diseases summarize cutting-edge advances developing expedite inflammation-related regenerative medicine engineering applications body systems. particular, pointed out challenges shortcomings that current ROS-sensitive materials encounter, offer distinctive insights into field present solutions improved strategies.

Язык: Английский

---

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

---