Naito Yuji, Akagiri Satomi, Uchiyama Kazuhiko, Kokura Satoshi, Yoshida Norimasa, Hasegawa Goji, Nakamura Naoto, Ichikawa Hiroshi, Toyokuni Shinya, Ijichi Tetsuo, Yoshikawa Toshikazu
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Biofactors. 2005;23(2):85-95. doi: 10.1002/biof.5520230204.
Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their non-diabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db/db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy.
氧化应激被认为是糖尿病引发肾病的一种重要机制。Oxykine是一种富含植物超氧化物歧化酶的哈密瓜提取物,其被小麦基质麦醇溶蛋白的聚合物薄膜所覆盖。在本研究中,我们使用2型糖尿病临床前啮齿动物模型,研究长期口服Oxykine是否能够预防由氧化应激诱导的糖尿病肾病进展。我们使用雌性db/db小鼠及其非糖尿病的db/m同窝小鼠。将小鼠分为以下三组:非糖尿病db/m;糖尿病db/db,以及用Oxykine治疗的糖尿病db/db。在实验过程中测量血糖水平、体重、尿白蛋白和尿8-羟基脱氧鸟苷(8-OHdG)。从治疗开始12周后进行组织学和8-OHdG免疫组织化学研究。治疗12周后,Oxykine治疗组和未治疗的db/db组之间的血糖水平和体重没有显著差异,然而两组均保持显著高于db/m小鼠的水平。与未治疗的db/db组相比,Oxykine治疗组通过系膜面积/总肾小球面积比计算的相对系膜面积得到显著改善。长期用Oxykine治疗可显著抑制治疗12周时尿白蛋白和8-OHdG的增加。未治疗的db/db小鼠肾小球中的8-OHdG免疫反应细胞比Oxykine治疗的db/db小鼠更多。在本研究中,Oxykine治疗改善了2型糖尿病啮齿动物模型糖尿病肾病的进展和加速。这些结果表明,Oxykine降低了糖尿病诱导的氧化应激和肾系膜细胞损伤。总之,Oxykine可能是预防糖尿病肾病的一种新方法。