Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(9), P. 7061 - 7070

Published: April 21, 2024

Language: Английский

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Nur77 Promotes Inflammation in Cisplatin‐Induced Acute Kidney Injury Through Transactivation of SERPINA3 Mediating Wnt/β‐Catenin Pathway

Nephrology, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 1, 2025

ABSTRACT Aim Acute kidney injury (AKI) is the most common complication in treatment of cisplatin, which a clinically effective and classical anticancer drug. Orphan Nuclear Receptor Nur77 has been found to promote renal ischaemia–reperfusion injury. In this study, we aim explore effects on cisplatin‐induced AKI (CI‐AKI) its underlying mechanism. Methods HK‐2 cells treated with cisplatin were used construct CI‐AKI model vitro. Cell viability cell proliferation analysed using CCK‐8 EdU assays, respectively. apoptosis was by flow cytometry. The inflammation release level detected ELISA. Molecular abundance evaluated qPCR, Western blot immunofluorescence. interaction between SERPINA3 clarified ChIP dual‐luciferase reporter gene assays. Results Our works demonstrated that expression considerably ascended cells. silence alleviated cisplatin‐stimulated injury, characterised increased proliferation, decreased inflammatory cytokine release. addition, promotes transcription binding promoter region (−182 −175), thereby upregulating activating Wnt/β‐catenin pathway. Moreover, induced notably inhibited knockdown Nur77. Furthermore, efficacy downregulation antagonised overexpression. Conclusion Taken together, our findings revealed resisted through lessening mediated transcriptional regulation inactivating

Language: Английский

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Short Hydration Regimen in Cisplatin-Based Chemotherapy and Its Impact on Nephrotoxicity: A Unicentric Prospective Study

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Nephrotoxicity is common when cisplatin used and hydration during treatment nephroprotective, but the optimal volume, composition, duration are unknown. We reviewed our institutional intravenous regimen (total 2500 mL in 5 hours versus previously 3000 7 hours) >50 mg/m2 schemes we aimed to confirm safety of this change by prospectively evaluating incidence acute kidney injury (AKI). included 105 patients cohort. However, for comparison, only considered 96 cases 191 controls (ratio 2:1), due impossibility matching all cases. The proportion without Kidney Disease Improving Global Outcomes (KDIGO) AKI stage ≥2 (serum creatinine ≥2.0-2.9 times baseline) was 100.0% (n=96) after first 97.8% (n=88) second There no difference compared with historical cohort who received previous (p=1 p=0.92 treatment). reason discontinuation three (2.9%). Our results support a shorter lower volume treatment, which more comfortable allows better health resource allocation.

Language: Английский

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Nebivolol rescued the liver and kidney from the coadministration of rivaroxaban and cisplatin by targeting inflammation, oxidative stress, and apoptosis in rats

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114486 - 114486

Published: March 19, 2025

Language: Английский

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Protocatechuic Acid Ameliorates Cisplatin-Induced Inflammation and Apoptosis in Mouse Proximal Tubular Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4115 - 4115

Published: April 26, 2025

Cisplatin is a highly cytotoxic drug used for the treatment of head, neck, and soft tissue cancers; however, it has nephrotoxic effects that can lead to acute kidney injury. Protocatechuic acid (PCA) natural widely available antioxidant found in many fruits such as kiwi, mango, berries. We have recently shown PCA reduced renal injury mouse model unilateral ureteral obstruction. The current study aims investigate protective Cisplatin-induced inflammation vitro Boston University Mouse Proximal Tubular (BUMPT) cells. BUMPT cells were cultured complete DMEM. Confluent then treated with 20 μM ± 50 or 100 24 h. showed dose-depending increase % cell viability Cisplatin-treated also dose-dependently decreased increases oxidative stress (ROS TBARS), (p-NF-κB IL-6), apoptosis (cleaved caspase-3 TUNEL+ cells) compared Cisplatin-only treatment. reduction stress, inflammation, was associated decreases tubular physical barrier resistance expression tight junction protein zonula occludens-1 (ZO-1) when alone. findings suggest improves function via reductions apoptosis.

Language: Английский

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Necroptosis and Its Involvement in Various Diseases

Advances in experimental medicine and biology, Journal Year: 2024, Volume and Issue: unknown, P. 129 - 143

Published: Jan. 1, 2024

Language: Английский

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Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

Molecules, Journal Year: 2024, Volume and Issue: 29(8), P. 1729 - 1729

Published: April 11, 2024

Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the polyphenol extract (referred to ZP) identified nine compounds, kaempferol chlorogenic acid, its composition. ZP shown promising properties an antioxidant anti-inflammatory agent. Our research revealed that protective effects against cisplatin-induced acute kidney injury (AKI). We comprehensive examination both pathological ultrastructural aspects found effectively ameliorated renal tissue lesions mitigated mitochondrial damage. Moreover, significantly suppressed malondialdehyde levels while increasing glutathione catalase concentrations kidneys AKI-induced mice. decreased number apoptotic cells pro-apoptotic protein expression mice human tubular epithelial (HK-2). Furthermore, treatment with increased proteins marking anti-ferroptosis, GPX4, FTH1, FSP1, experiments vivo vitro. elucidated underlying mechanisms ZP’s actions, revealing inhibitory effect on Yap phosphorylation regulation Lats expression, which exert influence kidneys. inhibiting Hippo pathway compromised nephroprotective vitro studies. summary, this shows exhibits renoprotective properties, reducing oxidative damage, apoptosis, ferroptosis by targeting pathway.

Language: Английский

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An overview on the protective effects of ellagic acid against heavy metals, drugs, and chemicals

Food Science & Nutrition, Journal Year: 2023, Volume and Issue: 11(12), P. 7469 - 7484

Published: Sept. 26, 2023

Abstract Ellagic acid (EA) is a polyphenol extracted from many plants. EA modulates inflammatory mediators via antioxidant mechanisms, such as catalase (CAT) activities, superoxide dismutase (SOD), enhancement, increase in glutathione (GSH), and lipid peroxidation (LPO) suppression. has anti‐apoptotic properties that are thought to be mediated by regulating the expression of B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), caspase‐3. In this article, we surveyed literature dealing with protective effects against different heavy metals, drugs, natural toxins. The findings indicated remarkable various toxicants. Its were mostly normalizing metabolism, oxidative stress, mediators, for example, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), IL‐1β. results study showed significant varied range compounds, either chemical or natural. These mainly intensifying defense system. However, other mechanisms inhibition responses suppression apoptosis important.

Language: Английский

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Cancer drugs and acute kidney injury: new therapies and new challenges

Current Opinion in Nephrology & Hypertension, Journal Year: 2024, Volume and Issue: 33(5), P. 474 - 485

Published: May 7, 2024

Purpose of review Cancer therapies continue to evolve at a rapid pace and although novel treatments, including immunotherapies targeted have allowed for substantial improvements in cancer survival, they carry associated risks acute kidney injury (AKI). We aim summarize the existing literature on AKI with spectrum systemic conventional chemotherapies, newer immunotherapies, growing number therapies, which may be both ‘pseudo-AKI’. Recent findings Conventional cytotoxic chemotherapies (e.g. cisplatin other platinum-based agents, methotrexate, pemetrexed, ifosfamide, etc.) well recognized nephrotoxicities (predominantly tubulointerstitial injury) remain widespread use. Immunotherapies (e.g., immune checkpoint inhibitors CAR-T therapies) immune-related adverse events, most often interstitial nephritis, rarely, glomerular disease. Recently, multiple been reduced renal tubular secretion creatinine, causing elevations serum creatinine apparent To complicate matters further, these agents had biopsy-proven, ‘true’ attributed them numerous case reports. Summary Clinicians nephrology oncology must aware various potential recognize those clinically meaningful impact outcomes.

Language: Английский

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Stepwise developmental mimicry generates proximal-biased kidney organoids

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range sugars, ions, amino acids, are highly susceptible to damage, leading pathologies necessitating dialysis transplants. While human pluripotent stem cell-derived organoids used modeling development, disease, injury, the formation proximal nephron cells in these 3D structures is incomplete. Here, we describe how drive development precursors following blueprint

Language: Английский

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