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Ameliorative Effects of Bredemolic Acid on Markers Associated with Renal Dysfunction in a Diet-Induced Prediabetic Rat Model.
Oxidative Medicine and Cellular Longevity ( IF 7.310 ) Pub Date : 2020-06-22 , DOI: 10.1155/2020/2978340
Akinjide Moses Akinnuga 1 , Angezwa Siboto 1 , Bongiwe Khumalo 1 , Ntethelelo Hopewell Sibiya 2 , Phikelelani Ngubane 1 , Andile Khathi 1
Affiliation  

Recently, studies have shown that renal dysfunction is associated not only with overt diabetes but also with the preceding stage known as prediabetes. Diet and pharmacological interventions are the therapeutic approaches to managing prediabetes, but the compliance in combining the two interventions is low. Hence, the efficacy of pharmacological intervention is reduced without diet modification. In our previous study, we established that bredemolic acid (BA) ameliorated glucose homeostasis via increased GLUT 4 expression in the skeletal muscle of prediabetic rats in the absence of diet intervention. However, the effects of bredemolic acid on renal function in prediabetic condition are unknown. Therefore, this study was aimed at investigating the ameliorative effects of bredemolic acid on renal dysfunction in a diet-induced prediabetic rat model. Thirty-six Sprague-Dawley male rats (150–180 g) were divided into two groups: the nonprediabetic () and prediabetic () groups which were fed normal diet (ND) and high-fat high-carbohydrate (HFHC) diet, respectively, for 20 weeks. After the 20th week, the prediabetic groups were subdivided into prediabetic control (PD) and 4 other prediabetic groups which were treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) for further 12 weeks (21st to 32nd). Plasma, urine, and kidney samples were collected for biochemical analysis. The untreated prediabetic (PD) rats presented increased fluid intake and urine output; increased creatinine, urea, and uric acid plasma concentrations; albuminuria; proteinuria; sodium retention; potassium loss; increased aldosterone and kidney injury molecule (KIM-1) concentration; and increased urinary podocin mRNA expression. However, BA administration attenuated the renal markers and oxidative stress and decreased the urinary podocin mRNA expression. In conclusion, BA administration, regardless of diet modification, attenuates renal dysfunction in an experimentally induced prediabetic state.

中文翻译:

在饮食诱导的糖尿病前期大鼠模型中,布雷多酸对肾功能不全相关标志物的改善作用。

最近,研究表明,肾功能不全不仅与明显的糖尿病有关,而且还与称为糖尿病的前期阶段有关。饮食和药物干预是治疗前驱糖尿病的治疗方法,但两种干预相结合的依从性较低。因此,如果不改变饮食,药理干预的功效就会降低。在我们以前的研究中,我们确定了在没有饮食干预的情况下,溴二酸(BA)通过增加GLUT 4在糖尿病前期大鼠骨骼肌中的表达来改善葡萄糖稳态。然而,在糖尿病前期,溴丁酸对肾功能的影响尚不清楚。因此,本研究旨在研究在饮食诱导的糖尿病前期大鼠模型中,溴丁酸对肾功能不全的改善作用。和糖尿病前期()的组分别接受正常饮食(ND)和高脂高碳水化合物(HFHC)饮食,持续20周。20后一周内,前驱糖尿病组分别细分为前驱糖尿病控制(PD)和将其用任一BA(80毫克/千克)或二甲双胍(MET,500毫克/千克)以进一步治疗12周4个其他前驱糖尿病组(21第一〜32)。收集血浆,尿液和肾脏样本进行生化分析。未经治疗的糖尿病前期(PD)大鼠的体液摄入量和尿量增加。肌酐,尿素和尿酸血浆浓度升高;蛋白尿 蛋白尿 钠retention留 钾损失 醛固酮和肾损伤分子(KIM-1)浓度增加;并增加尿中podocin mRNA表达。但是,BA给药减弱了肾脏标志物和氧化应激,并降低了尿Podocin mRNA表达。总之,无论饮食如何调整,BA给药都能在实验诱导的糖尿病前期状态下减轻肾功能不全。
更新日期:2020-06-22
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