The Effect of Quercetin for Salt Induces Renal Fibrosis by Suppressing Collagen Production

Widia Lestari, S. Rini
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Abstract

The bad effect of salt have been suspected for a least one hundred years. High salt intake increased production of TGF-β whereas TGF-β activates a receptor serine/threonine kinase (RS/TK). Through phosphorylation Smad2/3 and Co-Smad cascade, they recruited transcription factors and co-activator for initiates gene transcription for cell proliferation, cell differentiation, and extramatriks cellular production include collagen. This mechanism initiates renal fibrosis. This study was quasiexperimental research with post-test only group design. A subject was 24 male Wistar rat induced with two %/kgBB doses of NaCl 8%. The subjects were divided into six groups. NaCl 8% and quercetin were delivered by gavage daily for eight weeks. After treatment the kidneys were taken for quantification the collagen volume fraction were stained with picrosirius red then quantification by Image J software. The level of Glomerular volume collagen fraction group OO (3.78+0.12 %), NO (19.05+0.99 %), NK5 (19.42+3.19 %) NK10 (17.14+0.70 %) and NK20 (3.22+0.81). Tubular volume collagen fraction group OO (2.26+0.08 %), NO (9.79+0.53 %), NK5 (9.72+0.98 %), NK10 (5.25+0.49 %), NK20 (1.92+0.20 %). Our data indicate that quercetin may be suppressing the collage volume fraction with a significant difference in the dose of 20 mg/kg BB quercetin. Keyword: quercetin, TGF-β1, collagen volume fraction, NaCl, renal fibrosis. occurs over many months and years. Renal fibrosis is a significant cause of CKD (Chronic Kidney Disease) ended with ESRD (End Stage Renal Disease) can lead to organ dysfunction or death. The ESRD patient must do organ transplantation to improve the condition, but patients often die before take a suitable organ [3-6]. Preliminary research showed that 8% NaCl supplementation in Wistar Kyoto Rats for eight weeks increased the levels of TGF-β1 and collagen volume fraction in the kidney, left ventricle, and arterial intramyocardial without any significant increase in blood pressure [7]. Quercetin is a compound flavonol group of 6 flavonoid subclasses. Flavonoids are a group of compounds in plants that have the same molecular structure of flavones. Quercetin has antioxidant effects, inhibits protein kinase, inhibits DNA topoisomerase and regulate gene expression [9]. 10 mg/kg bodyweight quercetin may inhibit the left ventricular hypertrophy through the increased expression of PPARγ and inhibition of AP-1 signaling pathway. Histopathological test results also showed that the group of spontaneous hypersensitive Rats (SHR) were given therapy quercetin 10 mg / kgBB had the lowest volume of collagen [10]. The C57BL/6J rats are a renal interstitial fibrosis model showed decrease level of TGF-β significantly by giving thiazolidinedione as PPARγ agonist [11]. Administration of quercetin may provide a new discourse use of flavonoid compounds in protecting against renal fibrosis due to excessive salt intake. We need to evaluate the protective effects of quercetin as renoprotective with measured levels collagen volume fraction as a marker for the development of fibrosis in the kidney.
槲皮素对盐通过抑制胶原生成诱导肾纤维化的作用
人们怀疑盐的不良影响至少有一百年了。高盐摄入增加TGF-β的产生,而TGF-β激活丝氨酸/苏氨酸激酶受体(RS/TK)。通过磷酸化Smad2/3和Co-Smad级联,它们募集转录因子和共激活因子启动基因转录,用于细胞增殖、细胞分化和包括胶原在内的基质外细胞生成。这一机制引发肾纤维化。本研究为准实验研究,采用后验组设计。实验对象为24只雄性Wistar大鼠,以2% /kgBB剂量8% NaCl诱导。研究对象被分成六组。每日灌胃给予8% NaCl和槲皮素,连续8周。治疗后取肾脏定量,小天狼星红染色胶原体积分数,用Image J软件定量。肾小球体积胶原分数OO组(3.78+ 0.12%)、NO组(19.05+ 0.99%)、NK5组(19.42+ 3.19%)、NK10组(17.14+ 0.70%)、NK20组(3.22+0.81)。小管体积胶原蛋白分数组OO(2.26+ 0.08%)、NO(9.79+ 0.53%)、NK5(9.72+ 0.98%)、NK10(5.25+ 0.49%)、NK20(1.92+ 0.20%)。我们的数据表明槲皮素可能抑制拼贴体体积分数,剂量为20 mg/kg BB槲皮素差异显著。关键词:槲皮素,TGF-β1,胶原体积分数,NaCl,肾纤维化。发生在许多个月和几年。肾脏纤维化是CKD(慢性肾脏疾病)的一个重要原因,终末期肾脏疾病(ESRD)可导致器官功能障碍或死亡。ESRD患者必须进行器官移植以改善病情,但患者往往在接受合适的器官前死亡[3-6]。初步研究表明,Wistar Kyoto大鼠补充8% NaCl 8周后,肾脏、左心室和动脉心内动脉TGF-β1水平和胶原体积分数升高,但血压无明显升高[7]。槲皮素是6个类黄酮亚类的复合黄酮醇基团。黄酮类化合物是植物中具有与黄酮类化合物相同分子结构的一类化合物。槲皮素具有抗氧化作用,抑制蛋白激酶,抑制DNA拓扑异构酶,调节基因表达[9]。10 mg/kg体重槲皮素可能通过增加PPARγ的表达和抑制AP-1信号通路抑制左心室肥厚。组织病理学检测结果也显示,给予槲皮素10 mg / kgBB治疗的自发性超敏大鼠(SHR)胶原蛋白体积最低[10]。C57BL/6J肾间质纤维化模型大鼠给予噻唑烷二酮作为PPARγ激动剂后,TGF-β水平明显降低[11]。槲皮素的使用可能为黄酮类化合物在预防盐摄入过多引起的肾纤维化方面提供了新的论述。我们需要评估槲皮素作为肾保护的保护作用,测量胶原体积分数水平作为肾脏纤维化发展的标志。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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