From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1755 - 1755

Published: Feb. 1, 2024

This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in transition from acute kidney injury (AKI) disease (AKD) to chronic (CKD). It categorizes biomarkers AKI into stress, damage, functional markers, highlighting their importance early detection, prognosis, clinical applications. review also highlights links between renal pathophysiological mechanisms underlying AKD, including hypoperfusion, sepsis, nephrotoxicity, immune responses. In addition, various molecules play pivotal roles inflammation hypoxia, triggering maladaptive repair, mitochondrial dysfunction, system reactions, cellular senescence cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, Hippo/YAP/TAZ, promote fibrosis impact function. The renin-angiotensin-aldosterone (RAAS) triggers cascade leading fibrosis, with aldosterone exacerbating oxidative stress changes that fibrosis. evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed confirm full impact.

Language: Английский

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Modulating NLRP3 Inflammasomes in Idiopathic Pulmonary Fibrosis: A Comprehensive Review on Flavonoid-Based Interventions

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Idiopathic Pulmonary Fibrosis (IPF) is a severe, rapidly advancing disease that drastically diminishes life expectancy. Without treatment, it can progress to lung cancer. The precise etiology of IPF remains unknown, but inflammation and damage the alveolar epithelium are widely thought be pivotal in its development. Research has indicated activating NLRP3 inflammasome crucial mechanism pathogenesis, as triggers release pro-inflammatory cytokines such IL-1β, IL-18, TGF-β. These contribute myofibroblast differentiation extracellular matrix (ECM) accumulation. Currently, treatment options for limited. Only two FDA-approved medications, pirfenidone nintedanib, available. While these drugs decelerate progression, they come with range side effects do not cure disease. Additional strategies primarily involve supportive care therapy. Emerging research highlighted numerous flavonoids derived from traditional medicines inhibit critical regulators responsible inflammasome. show promise potential therapeutic agents managing IPF, offering new avenue targets core inflammatory processes this debilitating condition. Graphical

Language: Английский

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Metabolic reprogramming in septic acute kidney injury: pathogenesis and therapeutic implications

Metabolism, Journal Year: 2024, Volume and Issue: 158, P. 155974 - 155974

Published: July 10, 2024

Language: Английский

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The Role of Mitochondrial Sirtuins (SIRT3, SIRT4 and SIRT5) in Renal Cell Metabolism: Implication for Kidney Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6936 - 6936

Published: June 25, 2024

Kidney diseases, including chronic kidney disease (CKD), diabetic nephropathy, and acute injury (AKI), represent a significant global health burden. The kidneys are metabolically very active organs demanding large amount of ATP. They composed highly specialized cell types in the glomerulus subsequent tubular compartments which fine-tune metabolism to meet their numerous diverse functions. Defective renal metabolism, altered fatty acid oxidation or glycolysis, has been linked both AKI CKD. Mitochondria play vital role emerging research identified mitochondrial sirtuins (SIRT3, SIRT4 SIRT5) as key regulators metabolic adaptation, especially SIRT3. Sirtuins belong an evolutionarily conserved family mainly NAD

Language: Английский

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Reno-protective impact of diosmin and perindopril in amikacin-induced nephrotoxicity rat model: modulation of SIRT1/p53/C-FOS, NF-κB-p65, and keap-1/Nrf2/HO-1 signaling pathways

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Feb. 27, 2025

Amikacin (AMC), an aminoglycoside antibiotic known for its rapid and potent bactericidal activity, is also associated with nephrotoxicity. Diosmin perindopril have been reported to improve renal function hold promise as therapeutic agents preventing drug-induced This study aimed investigate the protective effect of perindopril, either alone or in combination, against damage induced by AMC toxicity elucidate underlying mechanisms. The researchers evaluated impact (50 mg/kg, orally) (2 intraperitoneally) on AMC-induced kidney injury (1.2 g/kg, rats. Invasive blood pressure, serum parameters, oxidative stress biomarkers, inflammatory cytokine levels tissue were assessed. Histopathological changes examined using hematoxylin eosin (H&E) staining, electron microscopy, immunohistochemical analysis. molecular mechanisms combination pretreatment investigated enzyme-linked immunosorbent assay (ELISA) Western blotting techniques. findings demonstrated that therapy improved attenuating pathological observed H&E staining including tubular necrosis glomerular damage, addition reducing creatinine compared group, urea nitrogen (BUN) uric acid, albumin. Mean arterial markers Kidney Injury Molecule-1 (KIM-1), Cystatin-c decreased samples group group. Furthermore, downregulated NF-κB-p65, P53, Keap-1, C-FOS, while upregulating Mammalian sirtuin 1 (SIRT1), inhibitor nuclear factor kappa B (Iκβ), erythroid 2-related 2 (Nrf2), Heme oxygenase-1 (HO-1) levels. reveal potential clinical application combining reduce nephrotoxicity, which requires further research settings.

Language: Английский

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Diosmin Alleviates Colitis by Inhibiting PANoptosis of Intestinal Epithelial Cells and Regulating Gut Microbiota and Metabolites

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156671 - 156671

Published: March 1, 2025

Language: Английский

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Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 30, 2024

Sirtuin 3 (SIRT3) belongs to the protein family, which consists of NAD

Language: Английский

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Role of diosmin in preventing doxorubicin-induced cardiac oxidative stress, inflammation, and hypertrophy: A mechanistic approach

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(6), P. 102103 - 102103

Published: May 15, 2024

Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug's clinical applications. Hence, this study intended investigate whether diosmin could prevent or limit in an animal setting. Thirty-two rats were separated into four distinct groups controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), 100 mg plus Dox, and 200 Dox. At end experiment, anesthetized sacrificed their blood hearts collected. Cardiac toxicity markers analyzed blood, heart tissue was by biochemical assays MDA, GSH, CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, COX-2), gene expression (β-MHC, BNP). Formalin-fixed for histopathological studies. We demonstrated that insult resulted increased oxidative stress, inflammation, hypertrophy shown MDA levels reduced GSH content CAT activity. Furthermore, treatment induced cardiac damage, evidenced analysis, ELISA, analysis. co-administration at both doses, mg, mitigated these alterations. Data derived from current research revealed cardioprotective effect likely due its ability mitigate stress inflammation. further is required protective effects against cardiotoxicity.

Language: Английский

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A therapeutic approach to identify leading molecules from natural products and therapeutic targets in CKD by network pharmacology

PharmaNutrition, Journal Year: 2024, Volume and Issue: unknown, P. 100421 - 100421

Published: Nov. 1, 2024

Language: Английский

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