Biochanin-A Protects Rats from Diabetes-associated Cardiorenal Damage by Attenuating Oxidative Stress through Activation of Nrf-2/HO-1 Pathway

P. P. Sethumathi, V. Uddandrao, P. Chandrasekaran, S. Sengottuvelu, P. Tamilmani, P. Ponmurugan, S. Vadivukkarasi, M. Santhanakumar, M. S. Begum, G. Saravanan
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Abstract

The current study is designed to evaluate the cardiorenal protective efficacy of the Biochanin-A (BCA) against high-fat-diet (HFD) and streptozotocin (STZ)-induced diabetes in rats. BCA (10mg/kg body weight) was administered to the diabetic rats for a period of 30 days and evaluated its effect on hyperglycemic markers, formation of lipid peroxidation, nitric oxide production and antioxidant enzymes such as superoxide dismutase, catalase and glutathione mediated enzymes. Further, we assessed the impact of BCA on nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) along with antioxidant enzymes mRNA expressions by RT-PCR. BCA administration to diabetic rats resulted in attenuation of hyperglycemia and oxidative stress in both the kidney and heart. Further, BCA enhanced the endogenous antioxidant activities in the kidney and heart and up-regulated their corresponding mRNA expressions. In addition, BCA treatment produced notable up-regulation of Nrf-2 and HO-1 mRNA expressions in the cardiac and renal tissue of diabetic rats. In conclusion, the current study revealed that BCA could protect from diabetes-induced complications such as cardiomyopathy and nephropathy by activating the Nrf-2/HO-1 pathway and enhancing the endogenous antioxidant state in the kidney and heart.
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生物茶素a通过激活Nrf-2/HO-1通路减轻氧化应激,保护大鼠免受糖尿病相关的心肾损伤
本研究旨在评价生物素a (BCA)对高脂饮食(HFD)和链脲佐菌素(STZ)诱导的糖尿病大鼠的心肾保护作用。采用BCA (10mg/kg体重)给药30 d,观察其对糖尿病大鼠高血糖指标、脂质过氧化反应形成、一氧化氮生成及超氧化物歧化酶、过氧化氢酶和谷胱甘肽介导酶等抗氧化酶的影响。此外,我们通过RT-PCR评估了BCA对核因子红系2相关因子-2 (Nrf-2)和血红素加氧酶-1 (HO-1)以及抗氧化酶mRNA表达的影响。BCA对糖尿病大鼠肾脏和心脏的高血糖和氧化应激均有抑制作用。BCA还能增强肾脏和心脏的内源性抗氧化活性,上调其mRNA的表达。此外,BCA处理显著上调糖尿病大鼠心脏和肾脏组织中Nrf-2和HO-1 mRNA的表达。综上所述,本研究表明BCA可以通过激活Nrf-2/HO-1通路,增强肾脏和心脏的内源性抗氧化状态,预防糖尿病引起的心肌病和肾病等并发症。
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