The Safety and Anti-Tumor Effects of Ozonated Water in Vivo

Kuroda, Kohei; Aso, Kazuo; Mori, Takuro; Kawamoto, Kinya; Murahata, Yusuke; Tsuka, Takeshi; Osaki, Tomohiro; Ito, Norihiko; Imagawa, Tomohiro; Itoh, Fumio; Okamoto, Yoshiharu

doi:10.3390/ijms161025108

Cited by 25 publications

(18 citation statements)

References 32 publications

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“…Regarding O 2 /O 3 therapy, evidence has been provided of the anti-cancer effect of local administration of ozonated water treatment in vitro and in vivo, in a mouse model of rectal cancer. The local treatment induced damages only in the tumor tissues by inducing necrosis without affecting normal tissues [ 43 ]. Moreover, the inhibitory effect of O 2 /O 3 treatment in two human neuroblastoma cell lines was analyzed [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Luongo¹,

Marinelli

Zeppa

et al. 2020

Cancers

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Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Luongo¹,

Marinelli

Zeppa

et al. 2020

Cancers

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“…Ozonated water is the liquid form generated when ozone is dissolved in saline, which is much easier to handle than the gaseous form. The safety and direct antitumor effect of ozonated water have been previously described by us ( 3 ).…”

Section: Introductionmentioning

confidence: 74%

Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment

et al. 2018

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Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the sensitivity of chemotherapy and radiation therapy. Ozone has been known to improve peripheral blood perfusion and oxygen partial pressure. The effect of ozonated water on tumor hypoxia, alone and in combination with an antitumor drug was studied in the present study. Following intraperitoneal administration of ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the intratumoral oxygen partial pressure was significantly increased. The tumor growth rate was more suppressed when ozonated water was combined with cisplatin (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells significantly decreased, whereas the number of TUNEL-positive cells significantly increased. The present study showed that ozonated water increased intratumoral blood perfusion and improved tumor hypoxia. In addition, ozonated water increased the therapeutic effect of CDDP. These findings, as well as previous reports, suggest that tumor growth is suppressed after treatment with ozonated water as the amount of CDDP reaching the tumor is increased when the intratumoral blood perfusion is increased due to the ozonated water. Thus, the administration of ozonated water may be a new therapeutic approach to solve current concerns regarding antitumor treatment.

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“…Another study in an animal model (tumor-bearing mouse model with rectal cancer) showed an antitumor effect of intratumor injection of ozonated water [ 31 ]. The effect was probably mediated by a local immunomodulation effect induced by ozone.…”

Section: Animal Modelsmentioning

confidence: 99%

Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

Clavo

Santana‐Rodríguez

Llontop

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Introduction This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment. Methods We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience. Results Over several decades, prestigious journals have published in vitro studies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy. Conclusions In vitro and animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.

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The Safety and Anti-Tumor Effects of Ozonated Water in Vivo

Cited by 25 publications

References 32 publications

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment

Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

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