Mechanistic and Molecular Insights into Empagliflozin’s Role in Ferroptosis and Inflammation Trajectories in Acetaminophen-Induced Hepatotoxicity

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 405 - 405

Опубликована: Март 13, 2025

Background: Acetaminophen (APAP)-induced acute liver injury (ALI) is increasingly becoming a public health issue with high rate of morbidity and mortality. Therefore, there critical demand for finding protective modalities by understanding the underlying proposed mechanisms including, but not limited to, ferroptosis inflammation. Objectives: This study seeks to investigate possible hepatoprotective effect empagliflozin (EMPA) against APAP-induced ALI through modulation inflammatory cascades. Methods: Mice were allocated into following five groups: vehicle control, APAP, EMPA 10, 20 (10 mg/kg/day, respectively, P.O.), N-acetylcysteine (NAC, agent ALI). The hepatic was detected determining enzymes histopathological examination. Inflammation, oxidative stress, apoptosis, also evaluated. Results: APAP group showed an elevated level disrupted architecture. toxicity promoted inflammation, ferroptosis, as indicated cytokines, lipid peroxidation, reduced antioxidants, increased caspase-3, decreased Bcl-2, activation NF-κB/STAT3/hepcidin pathway. Pretreatment remarkably reversed these features, which reflected restoration histoarchitecture tissue, higher dose more efficient. Conclusions: can induce initiation conditions, favor ferroptosis. hindered unfavorable consequences; outcome indicates its anti-inflammatory, antioxidant, anti-apoptotic, anti-ferroptotic effects. modulatory action advocated potential agent.

Язык: Английский

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Dietary retinoic acid improved the growth, lipid metabolism and immune status in Macrobrachium rosenbergii

Frontiers in Marine Science, Год журнала: 2025, Номер 12

Опубликована: Март 27, 2025

The effect of dietary retinoic acid (RA) on the growth, lipid deposition, oxidation resistance, immunity, hepatopancreatic and intestinal health Macrobrachium rosenbergii was evaluated. A total 1200 prawns (0.22 ± 0.00 g) were divided into six groups fed their corresponding feed containing 4, 132, 296, 562, 1206 or 2562 mg/kg RA. weight gain rate, specific growth rate final body changed linearly quadratically, with maximum observed in those 296 Increasing RA quadratically raised content whole body. Compared to 4 RA, there significantly lower deposition muscle, hepatopancreas Prawns had triglyceride (TG) upregulated gene expression retinoid X receptor ( RXR ), diacylglycerol acyltransferase 1 dgat1 ) carnitine palmitoyltransferase cpt1 ). Additionally, increased protein RXR, CAMKKβ phospho-AMPK. level could decrease oxidative stress by upregulating peroxiredoxin 5 prx5 improve immunity toll - like 2 toll2 myeloid differentiation factor 88 (myd88 dosal hepatopancreas. related genes crustin / 3 , anti-lipopolysaccharide 7 peritrophin-1 myosin light chain kinase claudin myd88 morphological structure also positively affected Furthermore, relieve immune responses induced lipopolysaccharide, thus leading transcription antimicrobial peptides. In summary, utilisation, antioxidant capacity M . To avoid negative effects excessive addition obtain optimal a diet suggested present study.

Язык: Английский

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Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity

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

Опубликована: Апрель 17, 2025

Язык: Английский

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Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets

Animal nutrition, Год журнала: 2024, Номер 16, С. 409 - 421

Опубликована: Янв. 21, 2024

Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability effective vaccines, development antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), metabolite vitamin A, has been shown to have anti-oxidative and properties. However, mechanism by which RA exerts its intestinal-protective effects on infection is not fully understood. The study investigates supplementation Duroc ×Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY were assigned into six treatments, including control group, treatment group two concentration gradients (5 15 mg/d), addition different mg/d). Our revealed that led extensive intestinal architecture damage, was mitigated at lower concentrations increasing villus height height/crypt depth ratio (P < 0.05), enhancing stem cell signaling promoting barrier functions. In addition, mg/d significantly increased NRF2 HO-1 protein expression 0.05) GSH content indicating can enhance redox homeostasis after Additionally, research demonstrated dual impact regulation autophagy, both stimulating initiation autophagy hindering flow autophagic flux. Through modulation flux, influence progression infection. These findings provide new insights hemostasis potential therapeutic application

Язык: Английский

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Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading

Acta Biochimica et Biophysica Sinica, Год журнала: 2023, Номер unknown

Опубликована: Ноя. 28, 2023

Acute liver failure (ALF) is a significant global issue with elevated morbidity and mortality rates. There an urgent pressing need for secure effective treatments. Ferroptosis, novel iron-dependent regulation of cell death, plays role in multiple pathological processes associated diseases, including ALF. Several studies have demonstrated that mesenchymal stem cells (MSCs) promising therapeutic potential the treatment This study aims to investigate positive effects MSCs against ferroptosis ALF model explore underlying molecular mechanisms their function. Our results show intravenously injected protect mouse models. decrease iron deposition mice by downregulating hepcidin level upregulating FPN1 level. labelled Dil are mainly observed hepatic sinusoid exhibit colocalization macrophage marker CD11b fluorescence. ELISA demonstrates high IGF1 CCL

Язык: Английский

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Cryptotanshinone Inhibits Bladder Cancer Cell Malignant Progression in a Lipopolysaccharide-Induced Inflammatory Microenvironment through NLRP3 Inhibition

Mediators of Inflammation, Год журнала: 2024, Номер 2024, С. 1 - 19

Опубликована: Янв. 30, 2024

Background. Bladder cancer (BC) is one of the most common malignancies urogenital system. This study assessed nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) in BC as well effects cryptotanshinone on changes malignant behaviors NLRP3 expression under a lipopolysaccharide (LPS)-induced inflammatory microenvironment. Methods. tissue specimens from 62 patients were collected for immunohistochemical detection protein. normal urothelial cell lines cultured mRNA Then, cells pretreated with LPS to mimic tumor Next, these incubated low or high dose assess its transfected cDNA confirm role vitro. Results. High was associated larger diameters (>2 cm), muscle invasion, metastasis. The levels greater than cells. pretreatment significantly promoted cytokine cells, induced viability, migration, invasion. However, able reduce LPS-induced increase progression. overexpression using further progression after stimulation reversed cryptotanshinone-reduced behaviors. Conclusion. might possess oncogenic activity BC, antitumor vitro be related inhibition expression.

Язык: Английский

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Considerations for Using Neuroblastoma Cell Lines to Examine the Roles of Iron and Ferroptosis in Neurodegeneration

Cells, Год журнала: 2024, Номер 13(18), С. 1541 - 1541

Опубликована: Сен. 13, 2024

Ferroptosis is an iron-dependent form of programmed cell death that influenced by biological processes such as iron metabolism and senescence. As brain levels increase with aging, ferroptosis also implicated in the development age-related pathologic conditions Alzheimer's disease (AD) related dementias (ADRD). Indeed, inhibitors have been shown to be protective models degenerative disorders like AD/ADRD. Given inaccessibility living human for metabolic studies, goal this work was characterize vitro model understanding how aging availability influence neuronal ferroptosis. First, (SH-SY5Y) mouse (Neuro-2a) neuroblastoma lines were terminally differentiated into mature neurons culturing all-trans-retinoic acid at least 72 h. Despite demonstrating all signs differentiation maturation, including increased expression storage protein ferritin, we discovered conferred resistance both lines. Gene data indicates their capacity protect against iron-mediated oxidative damage augmenting cystine import, subsequently increasing intracellular cysteine levels, promote glutathione production peroxidase activity (GPX). In support hypothesis, found cysteine-depleted media sensitized them GPX4 inhibition, these effects are mitigated supplementation. Such findings important they provide guidance use experimental investigate role neurodegeneration pathologies ADRD.

Язык: Английский

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Au/Ag@ZnS yolk-shell photocatalysts enhanced with noble metals and hyaluronic acid for efficient hydrogen production in rheumatoid arthritis therapy

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 280, С. 135929 - 135929

Опубликована: Сен. 24, 2024

Язык: Английский

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Mechanisms of Vitamins Inhibiting Ferroptosis

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1571 - 1571

Опубликована: Дек. 20, 2024

Ferroptosis is an iron-dependent form of cell death, which characterized by the uncontrolled and overwhelming peroxidation membrane lipids. has been implicated in progression various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, diabetes. Targeted inhibition ferroptosis provides a promising strategy to treat ferroptosis-related diseases. Multivitamins, vitamins A, B, C, D, E, K, have shown good ability inhibit ferroptosis. For example, vitamin A significantly upregulated expression several key ferroptotic gatekeepers genes through nuclear retinoic acid receptors X (RAR/RXR). Vitamin B6 could compensate for impaired glutathione (GSH) levels restore Glutathione peroxidase 4 (GPX4) cells, ultimately inhibiting D up-regulate anti-ferroptosis proteins activating receptors. E hydroquinone K (VKH2) can directly propagation lipid peroxidation, thereby In this review, we summarize currently understood mechanisms provide reference information future research on development inhibitors.

Язык: Английский

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Ecdysteroids-Enriched Fraction of Cyathula Officinalis K.C.Kuan Suppresses Synovial Proliferation and Inflammation to Ameliorate Ra by Inhibiting the Akt/Pi3k/Mtor Signalling Pathway

Опубликована: Янв. 1, 2024

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Язык: Английский

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