Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.
Cytotechnology. 2012 May;64(3):281-97. doi: 10.1007/s10616-011-9414-1. Epub 2011 Dec 6.
Insulin-producing cells express limited activities of anti-oxidative enzymes. Therefore, reactive oxygen species (ROS) produced in these cells play a crucial role in cytotoxic effects. Furthermore, diabetes mellitus (DM) development is closely linked to higher ROS levels in insulin-producing cells. Hita Tenryosui Water(®) (Hita T. W., Hita, Japan) and Nordenau water (Nord. W., Nordenau, Germany), referred to as natural reduced waters (NRWs), scavenge ROS in cultured cells, and therefore, might be a possibility as an alternative to conventional pharmacological agents against DM. Therefore, this study aimed to investigate the role of NRWs in alloxan (ALX)-induced β-cell apoptosis as well as in ALX-induced diabetic mice. NRWs equally suppressed DNA fragmentation levels. Hita T. W. and Nord. W. ameliorated ALX-induced sub-G(1) phase production from approximately 40% of control levels to 8.5 and 11.8%, respectively. NRWs restored serum insulin levels (p < 0.01) and reduced blood glucose levels (p < 0.01) in ALX-induced mice. Hita T. W. restored tissue superoxide dismutase (SOD) (p < 0.05) activity but not tissue catalase activity. Hita T. W. did not elevate SOD or catalase activity in HIT-T15 cells. Nord. W. restored SOD (p < 0.05) and catalase (p < 0.05) activity in both cultured cells and pancreatic tissue to normal levels. Even though variable efficacies were observed between Hita T. W. and Nord. W., both waters suppressed ALX-induced DM development in CD-1 male mice by administering NRWs for 8 weeks. Our results suggest that Hita T. W. and Nord. W. protect against ALX-induced β-cell apoptosis, and prevent the development of ALX-induced DM in experimental animals by regulating ALX-derived ROS generation and elevating anti-oxidative enzymes. Therefore, the two NRWs tested here are promising candidates for the prevention of DM development.
胰岛素分泌细胞表达有限的抗氧化酶活性。因此，这些细胞中产生的活性氧物质（ROS）在细胞毒性作用中起关键作用。此外，糖尿病（DM）的发展与胰岛素分泌细胞中更高的 ROS 水平密切相关。水素Tenryosui 水（Hita T.W.，日本日田）和诺登瑙水（Nord. W.，德国诺登瑙），被称为天然还原水（NRWs），可清除培养细胞中的 ROS，因此可能成为对抗 DM 的传统药物的替代品。因此，本研究旨在探讨 NRWs 在链脲佐菌素（ALX）诱导的β细胞凋亡以及 ALX 诱导的糖尿病小鼠中的作用。NRWs 同等抑制 DNA 片段化水平。Hita T.W. 和 Nord. W. 将 ALX 诱导的亚 G1 期产物从对照水平的约 40%分别改善至 8.5%和 11.8%。NRWs 恢复了血清胰岛素水平（p<0.01）并降低了 ALX 诱导的小鼠的血糖水平（p<0.01）。Hita T.W. 恢复了组织超氧化物歧化酶（SOD）（p<0.05）活性，但不恢复组织过氧化氢酶活性。Hita T.W. 未使 HIT-T15 细胞中的 SOD 或过氧化氢酶活性升高。Nord. W. 使培养细胞和胰腺组织中的 SOD（p<0.05）和过氧化氢酶（p<0.05）活性恢复正常水平。尽管 Hita T.W. 和 Nord. W. 之间观察到的疗效存在差异，但通过在 8 周内给予 NRWs，两种水都抑制了 CD-1 雄性小鼠的 ALX 诱导型糖尿病的发展。我们的结果表明，Hita T.W. 和 Nord. W. 通过调节 ALX 衍生的 ROS 生成和提高抗氧化酶来保护 ALX 诱导的β细胞凋亡，并防止实验动物中 ALX 诱导型 DM 的发展。因此，这里测试的两种 NRWs 是预防 DM 发展的有希望的候选物。
