Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 2, 2025

Background Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent their glucose-lowering effects. However, underlying mechanism remains unclear. This study hypothesized SGLT2i could alleviate diabetic injury by inhibiting ferroptosis and explored its potential mechanisms.

Language: Английский

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Sodium-Glucose-Cotransporter-2 Inhibitor Therapy and Intermitted Fasting in Cardiorenal Syndrome: The Role of Glucose-Mediated Oxidative Stress

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(3), P. 746 - 746

Published: Jan. 24, 2025

Cardiorenal syndrome (CRS) is a complex clinical disorder characterized by the interplay between heart and kidney dysfunction. This condition exacerbated comorbidities such as diabetes mellitus, which contribute to glucose-mediated oxidative stress, further complicating management of CRS. The CRS has evolved with discovery sodium-glucose-cotransporter-2 (SGLT2) inhibitors, have been established effective agents in reducing hyperglycemia demonstrated cardiorenal protective effects. Concurrently, intermittent fasting gained attention an intervention without pharmacological treatment for its metabolic benefits, including improved glucose metabolism insulin regulation sensitivity, both potential reduction stress. review provides summary current findings on roles SGLT2 inhibitors managing CRS, particular focus We evaluate mechanisms these interventions exert their effects, identify gaps research, offer recommendations future studies. While demonstrate more research needed elucidate long-term efficacy, safety, synergistic

Language: Английский

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Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Journal of Translational Internal Medicine, Journal Year: 2024, Volume and Issue: 12(1), P. 22 - 34

Published: Feb. 1, 2024

Abstract Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction malfunction. Although numerous studies on fibrosis have been carried out, underlying mechanism is largely unknown, no ideal treatment currently available. Ferroptosis an iron-dependent process of programmed cell death that characterized by lipid peroxidation. In the past decade, a growing body evidence demonstrated association between ferroptosis fibrotic diseases, while targeting may serve as potential therapeutic strategy. This review highlights recent advances crosstalk fibrosis, discusses ferroptosis-targeted approaches against are being explored.

Language: Английский

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Hepato-renal oxidative disturbances following acute β-adrenergic stimulation by isoprenaline in male Wistar rat: Attenuative role of taurine, a β-amino acid

Nutrire, Journal Year: 2024, Volume and Issue: 49(1)

Published: May 6, 2024

Language: Английский

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The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway

Biogerontology, Journal Year: 2024, Volume and Issue: 25(3), P. 567 - 581

Published: Feb. 26, 2024

Language: Английский

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Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study

BMC Pulmonary Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 20, 2024

Abstract Background The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed investigate causal association between type 1 (T1D), 2 (T2D), and IPF using Mendelian randomization (MR) analysis. Methods We used two-sample univariate multivariate MR (MVMR) analyses relationship T1D T2D IPF. obtained genome-wide (GWAS) data for from European Bioinformatics Institute, comprising 29,652 samples 101,101 single nucleotide polymorphisms (SNPs) 655,666 5,030,727 SNPs. also GWAS FinnGen Biobank 198,014 16,380,413 All cases controls in these datasets were derived exclusively populations. In analysis, we employed inverse variance-weighted (IVW), weighted median (WM), MR-Egger regression methods. For MVMR IVW method primarily, supplemented it with MR- least absolute shrinkage selection operator Heterogeneity tests conducted MR-IVW methods, whereas pleiotropic effects assessed intercept. results sensitivity visualized forest, scatter, leave-one-out, funnel plots. Results Univariate revealed a significant (OR = 1.118, 95% CI 1.021–1.225, P 0.016); however, no was found 0.911, 0.796–1.043, 0.178). analysis further confirmed 1.133, 1.011–1.270, 0.032), but 1.009, 0.790–1.288, 0.950). Sensitivity validated stability reliability our findings. Conclusion demonstrated IPF, evidence support Therefore, clinical practice, patients should undergo lung imaging early detection

Language: Английский

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Crosstalk between ferroptosis and autophagy: broaden horizons of cancer therapy

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Ferroptosis and autophagy are two main forms of regulated cell death (RCD). is a newly identified RCD driven by iron accumulation lipid peroxidation. Autophagy self-degradation system through membrane rearrangement. regulates the metabolic balance between synthesis, degradation reutilization cellular substances to maintain intracellular homeostasis. Numerous studies have demonstrated that both ferroptosis play important roles in cancer pathogenesis therapy. We also found there intricate connections autophagy. In this article, we tried clarify how different kinds participate process sort out common regulatory pathways cancer. By exploring complex crosstalk autophagy, hope broaden horizons

Language: Английский

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Emodin protects against severe acute pancreatitis-associated acute lung injury by activating Nrf2/HO-1/GPX4 signal and inhibiting ferroptosis in vivo and in vitro

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

Published: Feb. 5, 2025

Severe acute pancreatitis (SAP) has high morbidity, a complicated and dangerous course, many complications, including severe pulmonary complications. SAP-associated lung injury (SAP-ALI) is still significant challenge for surgeons because of its mortality. Therefore, more effective treatment methods are urgently needed. Emodin (EMO) shown tremendous potential in treating refractory diseases. However, protection mechanism SAP-ALI needs to be further clarified. This study was undertaken investigate the protective effects EMO against SAP rats alveolar epithelial cells, with particular focus on classical ferroptosis pathway. In an vivo study, forty SD were evenly split into five groups: sham operation (SO) group, biliopancreatic duct retrogradely injected 5% sodium taurocholate (STC) create + group administered via gavage following modeling, ML385 (a given inhibitor nuclear factor erythroid 2-related 2 (Nrf2)), group. vitro A549 cell lines exposed lipopolysaccharide (LPS) treated EMO. also used inhibit expression Nrf2. Pancreatic tissue damage evaluated using histological examination molecular experiments. Enzyme-linked immunosorbent assays (ELISA) assess levels pro-inflammatory cytokines, Fe2+, associated oxidative stress indicators serum supernatant. Real-time polymerase chain reaction (PCR), Western blot (WB), immunofluorescence find expressions related mRNAs proteins or cells. The findings demonstrated that suppressing Nrf2 exacerbated inflammatory response brought by pathological alterations SAP-ALI. reversed this change activating Nrf2/Heme Oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signal path. Moreover, these results showed EMO, contrary ML385, suppressed response, which manifested as up-regulated glutathione (GSH) GPX4 down-regulated malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) levels. Our effectively inhibited both vitro, while modulating Nrf2/HO-1/GPX4 signaling pathway provide

Language: Английский

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Research Progress on the Mechanism of Action of NRF2 in Pulmonary Fibrosis and Related Therapies

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(02), P. 536 - 545

Published: Jan. 1, 2025

Language: Английский

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Ferroptosis in organ fibrosis: Mechanisms and therapeutic approaches

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114341 - 114341

Published: March 1, 2025

Language: Английский

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