Protective mechanism of reduced water against alloxan-induced pancreatic β-cell damage:: Scavenging effect against reactive oxygen species
Protective mechanism of reduced water against alloxan-induced pancreatic β-cell damage:: Scavenging effect against reactive oxygen species
复制标题
DOI：
10.1023/a:1023936421448
复制
发表时间：
2002-01-01
期刊：
影响因子：
2.2
通讯作者：
Shirahata, S
中科院分区：
文献类型：
--
作者：
Li, YP;Nishimura, T;Shirahata, S
活性氧（reactive oxygen species，ROS）对生物大分子造成不可逆的损伤，导致多种疾病的发生。还原水（RW），例如富含氢的电解还原水和天然还原沃茨，如日本的Hita Tenryosui水和德国的诺尔德瑙水，已知其改善各种疾病，可以保护仓鼠胰腺β细胞系HIT-T15免受四氧嘧啶诱导的细胞损伤。四氧嘧啶是一种致糖尿病化合物，用于在动物中诱导1型糖尿病。其致糖尿病作用通过ROS的产生而发挥。四氧嘧啶处理的HIT-T15细胞表现出活力降低，细胞内ROS水平升高，胞浆游离Ca 2+浓度升高，DNA片段化，细胞内ATP水平降低和葡萄糖刺激的胰岛素释放降低。RW完全阻止了四氧嘧啶诱导的ROS的产生、胞浆Ca ~（2+）浓度的增加、胞内ATP水平的降低和葡萄糖刺激的胰岛素释放的降低，并强烈地阻断了DNA断裂，部分地抑制了四氧嘧啶处理的细胞活力的降低。RW使细胞内ATP水平和葡萄糖刺激的胰岛素分泌分别增加2-3.5倍和2-4倍，表明RW增强β细胞的葡萄糖敏感性和葡萄糖反应。RW的保护活性在4 ℃下保持一个月以上，但高压灭菌后丧失。这些结果表明RW通过防止四氧嘧啶衍生的活性氧产生来保护胰腺β细胞免受四氧嘧啶诱导的细胞损伤。RW可用于预防四氧嘧啶诱导的1型糖尿病。
Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules, resulting in many diseases. Reduced water (RW) such as hydrogen-rich electrolyzed reduced water and natural reduced waters like Hita Tenryosui water in Japan and Nordenau water in Germany that are known to improve various diseases, could protect a hamster pancreatic beta cell line, HIT-T15 from alloxan-induced cell damage. Alloxan, a diabetogenic compound, is used to induce type 1 diabetes mellitus in animals. Its diabetogenic effect is exerted via the production of ROS. Alloxan-treated HIT-T15 cells exhibited lowered viability, increased intracellular ROS levels, elevated cytosolic free Ca2+ concentration, DNA fragmentation, decreased intracellular ATP levels and lowering of glucose-stimulated release of insulin. RW completely prevented the generation of alloxan-induced ROS, increase of cytosolic Ca2+ concentration, decrease of intracellular ATP level, and lowering of glucose-stimulated insulin release, and strongly blocked DNA fragmentation, partially suppressing the lowering of viability of alloxan-treated cells. Intracellular ATP levels and glucose-stimulated insulin secretion were increased by RW to 2-3.5 times and 2-4 times, respectively, suggesting that RW enhances the glucose-sensitivity and glucose response of beta-cells. The protective activity of RW was stable at 4 degreesC for over a month, but was lost by autoclaving. These results suggest that RW protects pancreatic beta-cells from alloxan-induced cell damage by preventing alloxan-derived ROS generation. RW may be useful in preventing alloxan-induced type 1-diabetes mellitus.