{"title":"Emerging Therapeutic Potential of Fisetin for Nephrotoxicity, Kidney Injury, and Nephropathy: A Systematic Review.","authors":"Saeed Mohajeri, Alizamen Salehifard Jouneghani, Saeid Heidari-Soureshjani, Catherine Mt Sherwin, Faramarz Beigi","doi":"10.2174/0115733998369114250512094027","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction/objective: </strong>Kidney diseases cause high morbidity and mortality worldwide. This study investigated the mechanistic effects of Fisetin (FIS) on nephrotoxicity, kidney injury, and nephropathy induced by drugs, toxic chemicals, diabetes, lupus, diet, ureteral obstruction, and ischemic situations.</p><p><strong>Methods: </strong>To identify pertinent articles published before Oct 1, 2024, a comprehensive electronic search was performed across several databases, including MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus. After establishing clear inclusion and exclusion criteria, studies that met the research objectives were selected. Data were extracted and analyzed, documenting study characteristics, methodologies, and biological mechanisms.</p><p><strong>Results: </strong>Antioxidant benefits were evident with increased levels of endogenous antioxidant enzymes and NQO1, alongside reduced oxidative stress markers such as 8-OHdG and MDA. Enhanced mitochondrial function, including improved respiration, ATP synthesis, and antioxidant capacity, further supported cellular resilience. Anti-inflammatory effects were marked by reduced pro-inflammatory cytokines, macrophage and neutrophil infiltration, and inhibited pathways like NF-κB and MAPK. Anti-apoptotic actions included decreased levels of pro-apoptotic proteins. FIS also reduced fibrotic markers and pathways such as TGF-β/SMAD, mitigating excessive ECM buildup. Additionally, modulation of metabolic pathways was observed, including decreased glucose and lipid profiles and improved insulin sensitivity. Kidney function and structural integrity were preserved with reduced levels of nephrotoxic agents.</p><p><strong>Conclusion: </strong>Preclinical studies revealed that FIS demonstrates promising protective effects against kidney toxicity, renal injury, diabetes, and lupus-induced nephropathy. However, more clinical studies are needed in this field to determine effective and safe doses.</p>","PeriodicalId":10825,"journal":{"name":"Current diabetes reviews","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current diabetes reviews","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115733998369114250512094027","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction/objective: Kidney diseases cause high morbidity and mortality worldwide. This study investigated the mechanistic effects of Fisetin (FIS) on nephrotoxicity, kidney injury, and nephropathy induced by drugs, toxic chemicals, diabetes, lupus, diet, ureteral obstruction, and ischemic situations.
Methods: To identify pertinent articles published before Oct 1, 2024, a comprehensive electronic search was performed across several databases, including MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus. After establishing clear inclusion and exclusion criteria, studies that met the research objectives were selected. Data were extracted and analyzed, documenting study characteristics, methodologies, and biological mechanisms.
Results: Antioxidant benefits were evident with increased levels of endogenous antioxidant enzymes and NQO1, alongside reduced oxidative stress markers such as 8-OHdG and MDA. Enhanced mitochondrial function, including improved respiration, ATP synthesis, and antioxidant capacity, further supported cellular resilience. Anti-inflammatory effects were marked by reduced pro-inflammatory cytokines, macrophage and neutrophil infiltration, and inhibited pathways like NF-κB and MAPK. Anti-apoptotic actions included decreased levels of pro-apoptotic proteins. FIS also reduced fibrotic markers and pathways such as TGF-β/SMAD, mitigating excessive ECM buildup. Additionally, modulation of metabolic pathways was observed, including decreased glucose and lipid profiles and improved insulin sensitivity. Kidney function and structural integrity were preserved with reduced levels of nephrotoxic agents.
Conclusion: Preclinical studies revealed that FIS demonstrates promising protective effects against kidney toxicity, renal injury, diabetes, and lupus-induced nephropathy. However, more clinical studies are needed in this field to determine effective and safe doses.
简介/目的：肾脏疾病在世界范围内具有很高的发病率和死亡率。本研究探讨非西汀（FIS）对药物、有毒化学物质、糖尿病、狼疮、饮食、输尿管梗阻和缺血所致肾毒性、肾损伤和肾病的作用机制。方法：对MEDLINE/PubMed、Embase、Cochrane Library、Web of Science和Scopus等数据库进行全面的电子检索，以确定2024年10月1日之前发表的相关文章。在建立明确的纳入和排除标准后，选择符合研究目标的研究。提取和分析数据，记录研究特征、方法和生物学机制。结果：随着内源性抗氧化酶和NQO1水平的增加，以及8-OHdG和MDA等氧化应激标志物的降低，抗氧化效果明显。线粒体功能的增强，包括呼吸、ATP合成和抗氧化能力的改善，进一步支持了细胞的恢复能力。抗炎作用表现为减少促炎细胞因子、巨噬细胞和中性粒细胞浸润，抑制NF-κB和MAPK等通路。抗凋亡作用包括降低促凋亡蛋白水平。FIS还能减少纤维化标志物和TGF-β/SMAD等途径，减轻过度的ECM积聚。此外，代谢途径的调节被观察到，包括降低葡萄糖和脂质谱和改善胰岛素敏感性。肾毒性药物水平降低，肾脏功能和结构完整得以保留。结论：临床前研究显示，FIS对肾毒性、肾损伤、糖尿病和狼疮肾病具有良好的保护作用。然而，在这一领域需要更多的临床研究来确定有效和安全的剂量。
期刊介绍：
Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy. The journal"s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.
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