AMPK and NRF2: Interactive players in the same team for cellular homeostasis?

Free Radical Biology and Medicine, Год журнала: 2022, Номер 190, С. 75 - 93

Опубликована: Июль 31, 2022

NRF2 (Nuclear factor E2 p45‐related 2) is a stress responsive transcription lending cells resilience against oxidative, xenobiotic, and also nutrient or proteotoxic insults. AMPK (AMP-activated kinase), considered as prime regulator of cellular energy homeostasis, not only tunes metabolism to provide the cell at any time with sufficient ATP building blocks, but controls redox balance inflammation. Due observed overlapping responses upon activation common stressors impinging on both signaling, it plausible assume that signaling may interdepend cooperate readjust homeostasis. After short introduction two players this narrative review paints current picture how might interact molecular level, highlights their possible crosstalk in selected examples pathophysiology bioactivity drugs phytochemicals.

Язык: Английский

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Emerging trends in organ-on-a-chip systems for drug screening

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 13(6), С. 2483 - 2509

Опубликована: Фев. 15, 2023

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially pharmaceutical industry and healthcare services. Assessment efficacy safety prior human clinical trials crucial part development, which deserves greater emphasis reduce cost time in discovery. Recent advances microfabrication tissue engineering have given rise organ-on-a-chip, an

Язык: Английский

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Quinic acid alleviates liver toxicity induced by acetaminophen in mice via anti-oxidative and anti-inflammatory effects

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

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Mitochondrial Dysfunction and Chronic Liver Disease

Current Issues in Molecular Biology, Год журнала: 2022, Номер 44(7), С. 3156 - 3165

Опубликована: Июль 9, 2022

Mitochondria are generally considered the powerhouse of cell, a small subcellular organelle that produces most cellular energy in form adenosine triphosphate (ATP). In addition, mitochondria involved various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested different aspects, like increased mitochondrial reactive oxygen species (ROS), DNA (mtDNA) damage, (ATP) synthesis disorder, abnormal mitophagy, well changes morphology structure. related to occurrence development chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced injury (DILI), alcoholic fatty (AFL), non-alcoholic (NAFL). this review, we summarize discuss role mechanisms disease, focusing on discussing some latest studies disease.

Язык: Английский

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Pectolinarigenin ameliorates acetaminophen-induced acute liver injury via attenuating oxidative stress and inflammatory response in Nrf2 and PPARa dependent manners

Phytomedicine, Год журнала: 2023, Номер 113, С. 154726 - 154726

Опубликована: Фев. 24, 2023

Язык: Английский

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The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3067 - 3067

Опубликована: Фев. 4, 2023

Acute liver injury (ALI) is a globally important public health issue that, when severe, rapidly progresses to acute failure, seriously compromising the life safety of patients. The pathogenesis ALI defined by massive cell death in liver, which triggers cascade immune responses. Studies have shown that aberrant activation nod-like receptor protein 3 (NLRP3) inflammasome plays an role various types and NLRP3 causes programmed (PCD), these effectors can turn regulate activation. This indicates inextricably linked PCD. In this review, we summarize PCD (APAP, ischemia reperfusion, CCl4, alcohol, Con A, LPS/D-GalN induced ALI) analyze underlying mechanisms provide references for future relevant studies.

Язык: Английский

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Mitoquinone protects against acetaminophen-induced liver injury in an FSP1-dependent and GPX4-independent manner

Toxicology and Applied Pharmacology, Год журнала: 2023, Номер 465, С. 116452 - 116452

Опубликована: Март 7, 2023

Язык: Английский

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Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure

Biochemical Pharmacology, Год журнала: 2024, Номер 228, С. 116056 - 116056

Опубликована: Фев. 11, 2024

Liver injury and acute liver failure caused by an acetaminophen (APAP) overdose is a significant clinical problem in western countries. With the introduction of mouse model APAP hepatotoxicity 1970 s, fundamental mechanisms cell death were discovered. This included recognition that part dose metabolized cytochrome P450 generating reactive metabolite detoxified glutathione. After partial depletion glutathione, will covalently bind to sulfhydryl groups proteins, which initiating event toxicity. insight led N-acetyl-L-cysteine, glutathione precursor, as antidote against clinic. Despite substantial progress our understanding pathomechanisms over last decades viable new antidotes only emerged recently. review discuss background, action, prospects existing FDA-approved N-acetylcysteine, several drug candidates under development [4-methylpyrazole (fomepizole), calmangafodipir] examples additional therapeutic targets (Nrf2 activators) regeneration promoting agents (thrombopoietin mimetics, adenosine A2B receptor agonists, Wharton's Jelly mesenchymal stem cells). Although there are clear limitations certain approaches, reason be optimistic. The pathophysiology consideration drugs for recent years. Based on currently available information, it likely this result could used adjunct treatment N-acetylcysteine.

Язык: Английский

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NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(4), С. 1413 - 1435

Опубликована: Янв. 1, 2024

Caspase-11 detection of intracellular lipopolysaccharide mediates non-canonical pyroptosis, which could result in inflammatory damage and organ lesions various diseases such as sepsis.Our research found that lactate from the microenvironment acetaminophen-induced acute liver injury increased levels, enhanced gasdermin D activation accelerated macrophage lead to exacerbation injury.Further experiments unveiled inhibits ubiquitination by reducing its binding NEDD4, a negative regulator Caspase-11.We also identified lactates regulated NEDD4 K33 lactylation, protein interactions between NEDD4.Moreover, restraining lactylation reduces pyroptosis macrophages ameliorates injury.Our work links exquisite regulation inflammasome, provides basis for targeting signaling combat Caspase-11-mediated injury.

Язык: Английский

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Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Сен. 7, 2024

Язык: Английский

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