Biochemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia ; Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt.
Evid Based Complement Alternat Med. 2012;2012:580104. doi: 10.1155/2012/580104. Epub 2012 Sep 6.
The efficacy of Ferulsinaic acid (FA) to modulate the antioxidant enzymes and to reduce oxidative stress induced-diabetic nephropathy (DN) was studied. Rats were fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin; 5, 50 and 500 mg/kg of FA were administrated by oral intragastric intubation for 12 weeks. In FA-treated diabetic rats, glucose, kidney/body weight ratio, creatinine, BUN, albuminurea, and creatinine clearance were significantly decreased compared with non treated diabetic rats. Diabetic rats showed decreased activities of SOD and GSH; increased concentrations of malondialdehyde and IL-6 in the serum and kidney, and increased levels of 8-hydroxy-2'-deoxyguanosine in urine and renal cortex. FA-treatment restored the altered parameters in a dose-dependent manner. The ultra morphologic abnormalities in the kidney of diabetic rats were markedly ameliorated by FA treatment. Furthermore, FA acid was found to attenuate chronic inflammation induced by both Carrageenan and dextran in rats. We conclude that FA confers protection against injuries in the kidneys of diabetic rats by increasing activities of antioxidant enzymes and inhibiting accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.
研究阿魏酸(FA)对调节抗氧化酶和减少氧化应激诱导的糖尿病肾病(DN)的疗效。
大鼠给予富含蔗糖(50%,wt/wt)、猪油(30%,wt/wt)和胆固醇(2.5%,wt/wt)的饮食 8 周,以诱导胰岛素抵抗。用链脲佐菌素诱导 DN 模型后,通过口服灌胃给予 5、50 和 500mg/kg FA 12 周。与未治疗的糖尿病大鼠相比,FA 治疗的糖尿病大鼠的血糖、肾/体重比、肌酐、BUN、白蛋白尿和肌酐清除率显著降低。糖尿病大鼠血清和肾脏中的 SOD 和 GSH 活性降低,丙二醛和 IL-6 浓度增加,尿液和肾皮质中的 8-羟基-2'-脱氧鸟苷水平升高。FA 以剂量依赖性方式恢复了改变的参数。FA 处理明显改善了糖尿病大鼠肾脏的超微结构异常。此外,FA 酸还可减轻角叉菜胶和葡聚糖诱导的大鼠慢性炎症。
FA 通过增加抗氧化酶的活性和抑制肾脏中氧化 DNA 的积累,对糖尿病大鼠的肾脏损伤提供保护,提示其可能是预防和治疗 DN 的潜在药物。