Protective mechanism of reduced water against alloxan-induced pancreatic β-cell damage: Scavenging effect against reactive oxygen species

• Published in: Cytotechnology (Dordrecht) 2002-11, Vol.40 (1-3), p.139-149
• Main Authors: YUPING LI, NISHIMURA, Tomohiro, OSADA, Kazuhiro, KAWAHARA, Takeshi, OTSUBO, Kazumichi, MORISAWA, Shinkatsu, ISHII, Yoshitoki, GADEK, Zbigniew, SHIRAHATA, Sanetaka, TERUYA, Kiichiro, MAKI, Tei, KOMATSU, Takaaki, HAMASAKI, Takeki, KASHIWAGI, Taichi, KABAYAMA, Shigeru, SHIM, Sun-Yup, KATAKURA, Yoshinori
• Format: Article
• Language: English
• Subjects: Beta cells; Biological and medical sciences; Calcium (intracellular); Diabetes; Diabetes mellitus (insulin dependent); DNA fragmentation; Fundamental and applied biological sciences. Psychology; Glucose; Insulin; Insulin secretion; Intracellular; Macromolecules; Pancreas; Reactive oxygen species
• ISSN: 0920-9069; 1573-0778
• DOI: 10.1023/A:1023936421448

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 Ca(2+) 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 Ca(2+) 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 degrees C 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.