Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO‐1 pathway DOI
Xiaoliang Hua, Jiong Zhang, Juan Chen

et al.

The Prostate, Journal Year: 2024, Volume and Issue: 84(7), P. 666 - 681

Published: March 5, 2024

Abstract Background Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males loss of sperm quality. Current therapeutic options have failed achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role reducing inflammation, increasing antioxidant capacities, improving organ dysfunction; additionally NaB has good safety prospects great potential for clinical application. The purpose the current research was study effect on CP/CPPS underlying mechanisms using mouse model experimental autoimmune (EAP) mice. Methods EAP successfully established by subcutaneously injecting mixture prostate antigen complete Freund's adjuvant. Then, mice received daily intraperitoneal injections (100, 200, or 400 mg/kg/day) 16 days, from Days 26 42. We then explored anti‐inflammatory studying effects Nrf2 inhibitor ML385 HO‐1 zinc protoporphyrin inflammation this model. On Day 42, hematoxylin‐eosin staining dihydroethidium were used evaluate histological changes oxidative stress levels tissues. assessed applying Von Frey filaments lower abdomen. inflammation‐related cytokines, such as interleukin (IL)−1β, IL‐6, tumor necrosis factor detected enzyme‐linked immunosorbent assay. regulation Nrf2/HO‐1 signaling pathway expression NLRP3 inflammasome‐related protein western blot analysis Results Compared with group, development, manifestations, cytokine showed that reduced severity EAP. treatment could inhibit inflammasome activation. Mechanism studies intervention alleviate through signal pathway. inhibitors can ‐mediated stress. inhibitory activation also be blocked Conclusions alleviates prostatic associated inhibiting via an effective agent

Language: Английский

Regulated cell death pathways in kidney disease DOI Open Access
Ana B. Sanz, María Dolores Sánchez-Niño, Adrián M. Ramos

et al.

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(5), P. 281 - 299

Published: March 23, 2023

Language: Английский

Citations

162
Quercetin Ameliorates Diabetic Kidney Injury by Inhibiting Ferroptosis via Activating Nrf2/HO-1 Signaling Pathway DOI Creative Commons

Qi Feng,

Yang Yang,

Yingjin Qiao

et al.

The American Journal of Chinese Medicine, Journal Year: 2023, Volume and Issue: 51(04), P. 997 - 1018

Published: Jan. 1, 2023

Diabetic nephropathy (DN) is thought to be the major cause of end-stage renal disease. Due its complicated pathogenesis and low efficacy DN treatment, a deep understanding new etiological factors may useful. Ferroptosis, nonapoptotic form cell death, characterized by accumulation iron-dependent lipid peroxides lethal levels. Ferroptosis-triggered tubular injury reported participate in development DN, blocking ferroptosis might an effective strategy prevent DN. Quercetin (QCT), natural flavonoid that present variety fruits vegetables, has been ameliorate However, underlying nephroprotective mechanism unclear. Herein, we explored antiferroptosic effect QCT verified using mice high glucose (HG)-incubated epithelial models. We found HG-induced abnormal activation cells, treatment inhibited downregulating expression transferrin receptor 1 (TFR-1) upregulating glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH-1), cystine/glutamate reverse antiporter solute carrier family 7 member (SLC7A11) HG-incubated HK-2 cells. Subsequently, both vitro vivo results confirmed activated NFE2-related factor 2 (Nrf2)/Heme oxygenase-1(HO-1) signaling pathway increasing levels Nrf2 HO-1. Therefore, this study supports inhibits cells regulating Nrf2/HO-1 pathway, providing novel insight into protective treatment.

Language: Английский

Citations

75
Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation DOI Creative Commons

Zhiya Deng,

Man He,

Hongbin Hu

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(1), P. 151 - 165

Published: Aug. 31, 2023

AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff RTECs: renal tubular epithelial cells; SAKI: sepsis-induced Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.

Language: Английский

Citations

64
The Mechanisms of Ferroptosis Under Hypoxia DOI Creative Commons
Xīn Gào, Wei Hu, Dianlun Qian

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3329 - 3341

Published: July 17, 2023

Abstract Ferroptosis is a new form of programmed cell death, which characterized by the iron-dependent accumulation lipid peroxidation and increase ROS, resulting in oxidative stress death. Iron, lipid, multiple signaling pathways precisely control occurrence implementation ferroptosis. The mainly include Nrf2/HO-1 pathway, p62/Keap1/Nrf2 pathway. Activating pathway inhibits promotes Furthermore, some factors also participate ferroptosis under hypoxia, such as HIF-1, NCOA4, DMT1. Meanwhile, related with hypoxia-related diseases, MIRI, cancers, AKI. Accordingly, appears to be therapeutic target for diseases.

Language: Английский

Citations

58
GPX4, ferroptosis, and diseases DOI Open Access

Wangzheqi Zhang,

Yang Liu,

Liao Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

Citations

58
Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage DOI
Liang Huo, Chunfeng Liu,

Yujun Yuan

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115438 - 115438

Published: May 13, 2023

Language: Английский

Citations

54
Ferroptosis inhibitors: past, present and future DOI Creative Commons
Lei Zhang, Yi Luo, Yang Xiang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed mechanisms its formation continue to explore effective inhibitors in disease. Recent studies shown correlation between pathological neurodegenerative diseases, as well diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for treatment ferroptosis-mediated diseases. This article specifically describes metabolic pathways summarizes reported action natural synthetic small molecule their efficacy The paper also treatments such gene therapy, nanotechnology, summarises challenges encountered clinical translation inhibitors. Finally, relationship other modes discussed, hopefully paving way future drug design discovery.

Language: Английский

Citations

20
Quercetin improves diabetic kidney disease by inhibiting ferroptosis and regulating the Nrf2 in streptozotocin-induced diabetic rats DOI Creative Commons
Lei Zhang, Xingzhi Wang,

Liang Chang

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(1)

Published: March 11, 2024

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven tubular damage contributes to DKD's progression, making counteraction therapeutic strategy. Quercetin, flavonoid found numerous fruits and vegetables, has demonstrated DKD mitigation mouse models, though protective mechanism remains ambiguous. In this study, we delved quercetin's anti-ferroptotic properties, employing rat model high glucose (HG)-treated epithelial cell models. Our findings revealed HG prompted unusual ferroptosis activation cells. However, quercetin counteracted by inhibiting activating NFE2-related 2 (Nrf2) expression both rats HG-treated HK-2 cells, indicating role. Further experiments, vivo vitro, validated stimulates Nrf2. Thus, our research underscores modulating process via Nrf2 distinct model, offering fresh perspective on mechanisms.

Language: Английский

Citations

16
A new treatment approach: Melatonin and ascorbic acid synergy shields against sepsis-induced heart and kidney damage in male rats DOI
Hilal Üstündağ, Songül Doğanay, Ferdane Danışman Kalındemirtaş

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121875 - 121875

Published: June 23, 2023

Language: Английский

Citations

25
SAP130 released by ferroptosis tubular epithelial cells promotes macrophage polarization via Mincle signaling in sepsis acute kidney injury DOI Creative Commons
Jing Zhang, Jun Jiang, Bingqing Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 129, P. 111564 - 111564

Published: Feb. 5, 2024

The pathological mechanism of sepsis-associated acute kidney injury (SA-AKI) is complex and involves tubular epithelial cell (TEC) death immune activation. However, the interaction between macrophage-mediated inflammation remains unclear. In this study, we uncovered that TEC ferroptosis was activated in SA-AKI. Increased levels ferroptotic markers, including ferroptosis-related proteins, lipid peroxidation, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), reactive oxygen species (ROS), mitochondrial damage, were observed tissue cecum ligation puncture (CLP) Lipopolysaccharide (LPS)-induced SA-AKI mouse models, which subsequently suppressed by Ferrostatin-1 (Fer-1). vitro experiments showed Fer-1 inhibits LPS-induced Fe2+ accumulation, cytosolic ROS production. Moreover, it found induced promoted macrophage-inducible C-type lectin (Mincle) its downstream expression M1 polarization, mediated release spliceosome-associated protein 130 (SAP130), an endogenous ligand Mincle, from TEC. It confirmed supernatant LPS-stimulated TECs Mincle polarization macrophages. Further revealed macrophages aggravated ferroptosis, offset neutralizing SAP130 or inhibiting expression. addition, circulatory blunted expression, as well macrophage infiltration mice. conclusion, triggering Mincle/syk/NF-κB signaling, macrophages, turn, ferroptosis.

Language: Английский

Citations

16