Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Republic of Korea.
Mediators Inflamm. 2013;2013:510212. doi: 10.1155/2013/510212. Epub 2013 Apr 29.
Hyperglycemia-induced oxidative stress has been concerned in the development of diabetic nephropathy (DN), which may cause kidney damage associated with inflammation and fibrosis. This study has been conducted to investigate the role of genistein supplementation in an acute DN state. Mice with FBG levels more than 250 mg/dL after alloxan injection (single i.p., 150 mg/kg) were considered as diabetic. Diabetic mice (DM) were further subdivided according to their FBG levels, medium-high FBG (DMMH < 450 mg/dL) and high FBG (DMH; 450 mg/dL) and were administrated by an AIG-93G diet supplemented with different doses of genistein (0, 0.025 or 0.1%). After 2 weeks' treatment, the levels of kidney malondialdehyde (MDA), blood urea nitrogen (BUN), and plasma creatinine and lipid profiles, as well as oxidative stress and inflammation-related markers, were measured (P < 0.05). Genistein supplementation improved levels of FBG in the DMMH groups, but not in the DMH group, regardless of the treatment dose. Moreover, the supplementation attenuated kidney oxidative stress indicated by MDA, BUN, and plasma creatinine. In addition, genistein treatment decreased inflammatory markers such as nuclear factor kappa B (p65), phosphorylated inhibitory kappa B alpha, C-reactive protein, monocyte chemotactic protein-1, cyclooxygenase-2, and tumor necrosis factor-alpha and improved oxidative stress markers (nuclear-related factor E2, heme oxygenase-1, glutathione peroxidase, and superoxide dismutase isoforms) in treatment groups, regardless of the genistein treatment dose. Furthermore, genistein supplementation inhibited the fibrosis-related markers (protein kinase C, protein kinase C-beta II, and transforming growth factor-beta I) in the DN state. However, 0.1% genistein supplementation in diabetes with high FBG levels selectively showed a preventive effect on kidney damage. These results suggest that genistein might be a good protective substance for DN through regulation of oxidative stress and inflammation. In particular, genistein is more efficient in diabetes patients with medium-high blood glucose levels. Finally, it is required to establish the beneficial dosage of genistein according to blood glucose levels.
高血糖诱导的氧化应激与糖尿病肾病 (DN) 的发展有关，它可能导致与炎症和纤维化相关的肾脏损伤。本研究旨在探讨染料木黄酮补充在急性 DN 状态中的作用。经尾静脉注射（单次腹腔注射，150mg/kg）后血糖水平高于 250mg/dL 的小鼠被认为患有糖尿病。根据其血糖水平，进一步将糖尿病小鼠（DM）分为中高血糖（DMMH<450mg/dL）和高血糖（DMH；450mg/dL）组，并给予 AIG-93G 饮食补充不同剂量的染料木黄酮（0、0.025 或 0.1%）。治疗 2 周后，测量肾脏丙二醛（MDA）、血尿素氮（BUN）和血浆肌酐以及血脂谱水平，以及氧化应激和炎症相关标志物（P<0.05）。染料木黄酮补充剂改善了 DMMH 组的 FBG 水平，但对 DMH 组没有改善，无论治疗剂量如何。此外，补充剂减轻了 MDA、BUN 和血浆肌酐所指示的肾脏氧化应激。此外，染料木黄酮治疗降低了核因子 kappa B（p65）、磷酸化抑制 kappa B alpha、C-反应蛋白、单核细胞趋化蛋白-1、环氧合酶-2 和肿瘤坏死因子-α等炎症标志物，并改善了氧化应激标志物（核相关因子 E2、血红素加氧酶-1、谷胱甘肽过氧化物酶和超氧化物歧化酶同工酶），无论染料木黄酮的治疗剂量如何。此外，染料木黄酮补充抑制了纤维化相关标志物（蛋白激酶 C、蛋白激酶 C-β II 和转化生长因子-β I）在 DN 状态。然而，在高血糖水平的糖尿病中补充 0.1%染料木黄酮选择性地对肾脏损伤具有预防作用。这些结果表明，染料木黄酮可能通过调节氧化应激和炎症对糖尿病肾病有良好的保护作用。特别是，在血糖水平中等偏高的糖尿病患者中，染料木黄酮更为有效。最后，需要根据血糖水平确定染料木黄酮的有益剂量。
