Suppressive effects of natural reduced waters on alloxan-induced apoptosis and type 1 diabetes mellitus

Yuping Li, Takeki Hamasaki, Kiichiro Teruya, Noboru Nakamichi, Zbigniew Gadek, Taichi Kashiwagi, Hanxu Yan, Tomoya Kinjo, Takaaki Komatsu, Yoshitoki Ishii, Sanetaka Shirahata

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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-G1 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 antioxidative enzymes. Therefore, the two NRWs tested here are promising candidates for the prevention of DM development.

Original languageEnglish
Pages (from-to)281-297
Number of pages17
Issue number3
Publication statusPublished - May 2012

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Clinical Biochemistry
  • Cell Biology


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