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Renoprotective effect of calycosin in high fat diet-fed/STZ injected rats: Effect on IL-33/ST2 signaling, oxidative stress and fibrosis suppression.
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2019-11-11 , DOI: 10.1016/j.cbi.2019.108897
Nehal M Elsherbiny 1 , Eman Said 2 , Hoda Atef 3 , Sawsan A Zaitone 4
Affiliation  

Type 2 diabetes mellitus (T2DM) is a disease with a drastically growing worldwide prevalence. It is usually associated with numerous complications of which; diabetic nephropathy (DN); is a main complication of microvasculature and more seriously, a common cause of end-stage renal disease (ESRD). Unfortunately, both the lack of a definitive remedy alongside the economic and the social burden on DN patients enforces considerable impetus for developing alternative therapies. IL-33 is a newly discovered member of the IL-1 cytokine family. IL33/ST2 signaling plays a crucial role in acute and chronic kidney diseases. Calycosin is an isoflavone with reported IL33 signaling inhibitory activity. The present study aimed to investigate if calycosin possess renal protective effect in high-fat diet/STZ-induced T2DM model and to clarify the potential underlying mechanisms. HFD-STZ control rats showed functional and structural renal damage confirmed by increased serum creatinine, blood urea nitrogen and albuminuria associated with marked renal glomerulosclerosis and interstitial fibrosis. Initiation of inflammation, oxidative stress, and fibrosis was evident as depicted by elevated renal levels of IL33/ST2 mRNA as well as increased renal NF-κBp65, TNF-α, IL-1β, MDA, and TGF-β contents with suppressed Nrf2 and TAC. Calycosin treatment markedly improved the aforementioned makers of renal injury and dysfunction, modulated IL33/ST2 signaling, inflammatory cytokines, oxidative stress and fibrotic processes. This was accompanied by improvement of T2DM-induced renal ultramicroscopic and histopathological alterations.

中文翻译:

Calycosin在高脂饮食/ STZ注射大鼠中的肾脏保护作用:对IL-33 / ST2信号传导,氧化应激和纤维化抑制的影响。

2型糖尿病(T2DM)是一种在世界范围内普遍流行的疾病。它通常与许多并发症相关;糖尿病肾病(DN);是微血管系统的主要并发症,更严重的是终末期肾脏疾病(ESRD)的常见原因。不幸的是,缺乏明确的治疗措施以及对DN患者的经济和社会负担,都极大地推动了替代疗法的发展。IL-33是IL-1细胞因子家族的新成员。IL33 / ST2信号传导在急性和慢性肾脏疾病中起着至关重要的作用。Calycosin是一种异黄酮,具有报道的IL33信号抑制活性。本研究旨在调查在高脂饮食/ STZ诱导的T2DM模型中,calycosin是否具有肾脏保护作用,并阐明潜在的潜在机制。HFD-STZ对照大鼠显示出功能性和结构性肾损害,这与血清肌酐,血尿素氮和蛋白尿增加有关,并伴有明显的肾小球性肾小球硬化和间质纤维化。肾脏,IL33 / ST2 mRNA水平升高以及肾脏NF-κBp65,TNF-α,IL-1β,MDA和TGF-β含量升高,而Nrf2和Ng受到抑制,则表明炎症,氧化应激和纤维化的开始。交谘会。Calycosin治疗显着改善了上述肾脏损伤和功能障碍的产生者,调节了IL33 / ST2信号传导,炎性细胞因子,氧化应激和纤维化过程。
更新日期:2019-11-11
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