An enzyme-mimicking reactive oxygen species scavenger targeting oxidative stress-inflammation cycle ameliorates IR-AKI by inhibiting pyruvate dehydrogenase kinase 4 DOI Creative Commons
Wenfang He, Chenguang Ding, Ting Lin

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(19), P. 7534 - 7553

Published: Nov. 4, 2024

Rationale: Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant anti-inflammatory pathways disrupt stress-inflammation cycle IR-AKI. Methods: UV-vis absorption spectra, FTIR TEM were employed determine successful construction of CF@P. ABTS, TMB, NBT analyses performed detect ability enzyme-mimicking vitro vitro, antioxidant/anti-inflammatory effect CF@P detected MTT, qPCR, fluorescence, flow cytometry. Multi-omics revealed mechanism IR-AKI therapy, molecular docking further used mechanism. MRI photoacoustic imaging explore dual-mode capacity management. Results: could stress-inflammatory cascade scavenging ROS, reducing pro-inflammatory cytokines, modulation macrophage polarization. Subsequent multi-omics indicated that protective effects may be attributed inhibition pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated improve production compounds reduce nephrotoxicity. Additionally, exhibited promising capabilities T1-MRI for AKI Conclusions: Collectively, CF@P, possessing properties inhibiting PDK4, as well superior biocompatibility, holds promise therapeutic strategy

Language: Английский

Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease DOI Creative Commons
Miguel Fontecha‐Barriuso,

Ana M. López-Diaz,

Juan Guerrero‐Mauvecin

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(7), P. 1356 - 1356

Published: July 12, 2022

Acute kidney injury (AKI) and chronic disease (CKD) are interconnected conditions, CKD is projected to become the fifth leading global cause of death by 2040. New therapeutic approaches needed. Mitochondrial dysfunction oxidative stress have emerged as drivers in acute settings, promoting AKI-to-CKD transition. In this work, we review role mitochondrial AKI progression discuss novel approaches. Specifically, evidence for diverse models (nephrotoxicity, cytokine storm, ischemia-reperfusion injury) (diabetic disease, glomerulopathies) discussed; clinical implications information on key mitochondria-related transcriptional regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha, transcription factor EB (PGC-1α, TFEB), carnitine palmitoyl-transferase 1A (CPT1A) addressed; current status development targeting mitochondria updated; barriers mitochondria-targeted interventions discussed, including lack diagnostic tests that allow us categorize baseline renal dysfunction/mitochondrial monitor its response intervention. Finally, milestones further research proposed.

Language: Английский

Citations

62
An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management DOI

Caroline Assunção Oliveira,

Érika Azenathe Barros Mercês,

Fernanda Santos Portela

et al.

Clinical and Experimental Nephrology, Journal Year: 2024, Volume and Issue: 28(8), P. 711 - 727

Published: April 27, 2024

Language: Английский

Citations

9
Recent Advances in Nanomaterials for the Treatment of Acute Kidney Injury DOI

Xiaozhuo Ba,

Ye Tao,

Haojie Shang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(10), P. 12117 - 12148

Published: Feb. 29, 2024

Acute kidney injury (AKI) is a serious clinical syndrome with high morbidity, elevated mortality, and poor prognosis, commonly considered "sword of Damocles" for hospitalized patients, especially those in intensive care units. Oxidative stress, inflammation, apoptosis, caused by the excessive production reactive oxygen species (ROS), play key role AKI progression. Hence, investigation effective safe antioxidants inflammatory regulators to scavenge overexpressed ROS regulate inflammation has become promising therapeutic option. However, unique physiological structure complex pathological alterations kidneys render traditional therapies ineffective, impeding residence efficacy most antioxidant anti-inflammatory small molecule drugs within renal milieu. Recently, nanotherapeutic interventions have emerged as prospective strategy AKI, overcoming treatment dilemmas through size, shape, charge, surface modifications. This Review succinctly summarizes latest advancements approaches encompassing nanozymes, scavenger nanomaterials, MSC-EVs, nanomaterials loaded regulator. Following this, strategies aimed at enhancing biocompatibility targeting are introduced. Furthermore, brief discussion on current challenges future prospects this research field presented, providing comprehensive overview evolving landscape AKI.

Language: Английский

Citations

8
Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients DOI Creative Commons
Kranti A. Mapuskar,

G Vasquez Martinez,

Casey Pulliam

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 60, P. 102599 - 102599

Published: Jan. 3, 2023

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute chronic disease (AKD CKD, respectively). We conducted a retrospective analysis of renal function injury-related plasma biomarkers in subset HNSCC subjects receiving hdCis-RT double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. found that 90 mg AVA treatment prevented significant reduction estimated glomerular filtration rate (eGFR) three months as well six twelve after compared 30 placebo. Moreover, may have allowed repair first 22 days following evidenced by increase epithelial growth factor (EGF), known aid recovery. An upward trend was also observed iron homeostasis proteins including total (Fe-blood) saturation (Fe-saturation) group versus These data support hypothesis mitigates cisplatin-induced CKD inhibiting hdCis-induced changes promoting

Language: Английский

Citations

13
The underlying mechanisms of cisplatin-induced nephrotoxicity and its therapeutic intervention using natural compounds DOI
Doudou Zhang, Guangwen Luo,

Kaixiang Jin

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2023, Volume and Issue: 396(11), P. 2925 - 2941

Published: June 8, 2023

Language: Английский

Citations

13
A renal-targeted gene delivery system derived from spermidine for arginase-2 silencing and synergistic attenuation of drug-induced acute kidney injury DOI

Xurui Gu,

Kun Liu, Yixuan Deng

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 486, P. 150125 - 150125

Published: March 3, 2024

Language: Английский

Citations

5
Cisplatin Nephrotoxicity: Novel Insights Into Mechanisms and Preventative Strategies DOI
Shveta S. Motwani,

Sharneet Sandhu Kaur,

Abhijat Kitchlu

et al.

Seminars in Nephrology, Journal Year: 2022, Volume and Issue: 42(6), P. 151341 - 151341

Published: Nov. 1, 2022

Language: Английский

Citations

20
Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury DOI Creative Commons
Kranti A. Mapuskar, Casey Pulliam, Diana Zepeda‐Orozco

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1728 - 1728

Published: Sept. 6, 2023

Cisplatin, a potent chemotherapeutic agent, is marred by severe nephrotoxicity that governed mechanisms involving oxidative stress, inflammation, and apoptosis pathways. The transcription factor Nrf2, pivotal in cellular defense against stress the master regulator of antioxidant response, upregulating antioxidants cytoprotective genes under stress. This review discusses underlying chemotherapy-induced kidney injury, focusing on role Nrf2 cancer therapy its redox regulation cisplatin-induced injury. We also explore Nrf2's signaling pathways, post-translational modifications, involvement autophagy, as well examine redox-based strategies for modulating injury while considering limitations potential off-target effects modulation. Understanding holds significant promise developing novel therapeutic interventions. knowledge could provide valuable insights into mitigating associated with cisplatin, ultimately enhancing safety efficacy treatment.

Language: Английский

Citations

11
Kynurenine 3-monooxygenase limits de novo NAD+ synthesis through dietary tryptophan in renal proximal tubule epithelial cell models DOI
Yougang Zhai, Jose A. Chavez, Katharine D’Aquino

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. C1423 - C1436

Published: March 18, 2024

Nicotinamide adenine dinucleotide (NAD + ) is essential in regulating mitochondrial function. Reduced NAD synthesis through the de novo pathway associated with acute kidney injury (AKI). Our study reveals a disruption proximal tubular models, but not vivo, attributed to downregulation of enzyme kynurenine 3-monooxygenase (KMO). These findings highlight crucial role KMO governing biosynthesis within kidney, shedding light on potential AKI interventions.

Language: Английский

Citations

4
Chemoprotective Mechanism of Sodium Thiosulfate Against Cisplatin-Induced Nephrotoxicity Is via Renal Hydrogen Sulfide, Arginine/cAMP and NO/cGMP Signaling Pathways DOI Open Access
George J. Dugbartey, Karl K. Alornyo, Ismaila Adams

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 384 - 384

Published: Jan. 4, 2025

Cisplatin is a common and highly effective chemotherapeutic agent whose nephrotoxic side effect well-characterized. Sodium thiosulfate (STS), an FDA-approved hydrogen sulfide (H2S) donor drug, emerging as chemoprotective against cisplatin-induced nephrotoxicity (CIN). In this study, we investigated the mechanism of STS in rat model CIN. Twenty-five male Sprague Dawley rats were randomly assigned to following groups: HC: Healthy control (received 10 mL/kg/day 0.9% saline intraperitoneally (ip), [n = 5]), CIN: single dose 7 mg/kg cisplatin ip 5]); CIN + PAG: daily administration 40 H2S inhibitor, DL-propargylglycine (PAG) for 28 days (n 5); PAG STS: (150 µM) injection days; 5). Rats each group kept metabolic cages 24 h on day 0, 14 29 after urine collection. then euthanized, kidney blood samples collected analysis. Histologically, was characterized by glomerular tubular injury significant macrophage influx apoptosis, well markedly increased levels plasma renal IL-1β, IL-6 TNF-α impaired antioxidant status compared HC (p < 0.001). These pathological changes exacerbated strongly reduced relative 0.01), while superior protection observed rats. Functionally, evidenced serum creatinine BUN, significantly decreased creatinine, clearance, electrolyte imbalance urinary concentrating defect comparison with 0.01). functional worsened 0.05) but improved rats, further improvement comparable Mechanistically, H2S, arginine, cAMP, nitric oxide (NO) cGMP SIRT3 PGC-1α. We have shown first time that provides chemoprotection activating arginine/cAMP NO/cGMP signaling pathways their downstream mechanisms through production.

Language: Английский

Citations

0