{"title":"Hinokitiol Prevents Diabetic Acute Kidney Injury by Mitigating ER Stress.","authors":"Tahib Habshi, Hrushikesh Kulkarni, Neha Dagar, Vishwadeep Shelke, Anil Bhanudas Gaikwad","doi":"10.1002/cbin.70008","DOIUrl":null,"url":null,"abstract":"<p><p>Acute kidney injury (AKI) in diabetic conditions often advances to chronic kidney disease (CKD), exacerbated by ischemia-reperfusion injury (IRI) through pathomechanisms such as endoplasmic reticulum (ER) stress and inflammation. Currently, available treatment options for diabetic AKI are not uniformly effective, highlighting the need for novel interventions. This study aimed to examine the renoprotective effects of hinokitiol, a natural tropolone compound, against diabetic AKI with its capability to decrease ER stress and inflammation, along with apoptosis. This study involved NRK-52E cells grown in-vitro under high-glucose conditions subjected to 10 mM sodium azide to elicit hypoxia/reperfusion injury (HRI). The expression of key ER stress markers like binding immunoglobulin binding protein (BiP), R/PKR-like ER kinase (PERK), and eukaryotic initiation factor-2 (eIF2α) as well as inflammatory proteins was markedly diminished by hinokitiol pretreatment (50 μM). Hinokitiol further reduced apoptosis in the NRK-52E cells. Similarly, in the in-vivo study, male Wistar rats with STZ-induced Type 1 diabetes (55 mg/kg, i.p.) were treated with hinokitiol 50 and 100 mg/kg/day i.p. for 5 days, followed by AKI induction via bilateral IRI. Hinokitiol pretreatment significantly reduced the elevated plasma blood urea nitrogen (BUN), creatinine, and urinary kidney injury molecule-1 (KIM-1) levels and tubular damage in diabetic AKI rats. Hinokitiol also reduced the respective ER stress protein expressions in diabetic AKI rats, as demonstrated by immunohistochemical analysis and immunoblotting. These findings suggest that hinokitiol alleviates diabetic AKI by modulating the PERK/CHOP/NF-κB axis, highlighting the likeliness of hinokitiol as a viable therapeutic technique for alleviating diabetic AKI.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbin.70008","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Acute kidney injury (AKI) in diabetic conditions often advances to chronic kidney disease (CKD), exacerbated by ischemia-reperfusion injury (IRI) through pathomechanisms such as endoplasmic reticulum (ER) stress and inflammation. Currently, available treatment options for diabetic AKI are not uniformly effective, highlighting the need for novel interventions. This study aimed to examine the renoprotective effects of hinokitiol, a natural tropolone compound, against diabetic AKI with its capability to decrease ER stress and inflammation, along with apoptosis. This study involved NRK-52E cells grown in-vitro under high-glucose conditions subjected to 10 mM sodium azide to elicit hypoxia/reperfusion injury (HRI). The expression of key ER stress markers like binding immunoglobulin binding protein (BiP), R/PKR-like ER kinase (PERK), and eukaryotic initiation factor-2 (eIF2α) as well as inflammatory proteins was markedly diminished by hinokitiol pretreatment (50 μM). Hinokitiol further reduced apoptosis in the NRK-52E cells. Similarly, in the in-vivo study, male Wistar rats with STZ-induced Type 1 diabetes (55 mg/kg, i.p.) were treated with hinokitiol 50 and 100 mg/kg/day i.p. for 5 days, followed by AKI induction via bilateral IRI. Hinokitiol pretreatment significantly reduced the elevated plasma blood urea nitrogen (BUN), creatinine, and urinary kidney injury molecule-1 (KIM-1) levels and tubular damage in diabetic AKI rats. Hinokitiol also reduced the respective ER stress protein expressions in diabetic AKI rats, as demonstrated by immunohistochemical analysis and immunoblotting. These findings suggest that hinokitiol alleviates diabetic AKI by modulating the PERK/CHOP/NF-κB axis, highlighting the likeliness of hinokitiol as a viable therapeutic technique for alleviating diabetic AKI.
期刊介绍:
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.