The Safety and Anti-Tumor Effects of Ozonated Water in Vivo.
Ozonated water is easier to handle than ozone gas. However, there have been no previous reports on the biological effects of ozonated water. We conducted a study on the safety of ozonated water and its anti-tumor effects using a tumor-bearing mouse model and normal controls. Local administration of ozonated water (208 mM) was not associated with any detrimental effects in normal tissues. On the other hand, local administration of ozonated water (20.8, 41.6, 104, or 208 mM) directly into the tumor tissue induced necrosis and inhibited proliferation of tumor cells. There was no significant difference in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL)-positive cells following administration of ozonated water. The size of the necrotic areas was dependent on the concentration of ozonated water. These results indicate that ozonated water does not affect normal tissue and damages only the tumor tissue by selectively inducing necrosis. There is a possibility that it exerts through the production of reaction oxygen species (ROS). In addition, the induction of necrosis rather than apoptosis is very useful in tumor immunity. Based on these results, we believe that administration of ozonated water is a safe and potentially simple adjunct or alternative to existing antineoplastic treatments.
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. nanararayu@gmail.com.
Kohei
K
Kuroda
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. kazu-azuma@muses.tottori-u.ac.jp.
Kazuo
K
Azuma
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. t_k_low15@yahoo.co.jp.
Takuro
T
Mori
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. kawamotokinya@yahoo.co.jp.
Kinya
K
Kawamoto
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. ymurahata@muses.tottori-u.ac.jp.
Yusuke
Y
Murahata
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. tsuka@muses.tottori-u.ac.jp.
Takeshi
T
Tsuka
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. tosaki@muses.tottori-u.ac.jp.
Tomohiro
T
Osaki
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. taromobile@me.com.
Norihiko
N
Ito
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. imagawat@muses.tottori-u.ac.jp.
Tomohiro
T
Imagawa
Department of Technical Development, Sakuragawa Pump Co., Ltd., Osaka 567-0005, Japan. itoh@sakura-p.net.
Fumio
F
Itoh
Department of Clinical Medicine, Joint School of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. yokamoto@muses.tottori-u.ac.jp.
Yoshiharu
Y
Okamoto
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000473:pathology*; D010100:Oxygen / Q000737:chemistry; D010126:Ozone / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014867:Water / Q000737:chemistry*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D014867:Water; D010126:Ozone; D004253:DNA Nucleotidylexotransferase; D010100:Oxygen
anti-tumor effect; ozonated water; ozone; reactive oxygen species