Therapeutic potential of ozone water treatment in alleviating atopic dermatitis symptoms in mouse models: Exploring its bactericidal and direct anti-inflammatory properties

Mao Kaneki; Chiharu Ohira; Miyu Takahashi; Naoki Iwashita; Yoshiichi Takagi; Masaki Nagane; Jumpei Uchiyama; Tomoki Fukuyama

doi:10.1016/j.intimp.2023.110920

Therapeutic potential of ozone water treatment in alleviating atopic dermatitis symptoms in mouse models: Exploring its bactericidal and direct anti-inflammatory properties

Int Immunopharmacol. 2023 Nov;124(Pt A):110920. doi: 10.1016/j.intimp.2023.110920. Epub 2023 Sep 14.

Authors

Mao Kaneki¹, Chiharu Ohira¹, Miyu Takahashi¹, Naoki Iwashita², Yoshiichi Takagi³, Masaki Nagane⁴, Jumpei Uchiyama⁵, Tomoki Fukuyama⁶

Affiliations

¹ Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan.
² Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan; Bioalch Co. Ltd., 3-28 Honshuku-cho, Fuchu-shi, Tokyo, Japan.
³ Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan; Japan SLC Inc, 85 Ohara-cho, Kita-ku, Hamamatsu-shi, Shizuoka, Japan.
⁴ Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan; Center for Human and Animal Symbiosis Science, Azabu University, Sagamihara, Kanagawa, Japan.
⁵ Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
⁶ Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan; Center for Human and Animal Symbiosis Science, Azabu University, Sagamihara, Kanagawa, Japan. Electronic address: t-fukuyama@azabu-u.ac.jp.

PMID: 37716162
DOI: 10.1016/j.intimp.2023.110920

Abstract

Currently, ozone water is utilized for antibacterial and antiviral purposes without any reported safety concerns. Therefore, ozone water may have clinical applications in treating staphylococcal-specific cutaneous diseases, such as atopic dermatitis (AD) and pyoderma. This study aimed to verify the bactericidal effects of ozone water at different concentrations (3 and 11 mg/L) against staphylococcal species in vitro, as well as evaluate the anti-inflammatory effects of ozone water in a mouse model of AD and pyoderma. Initially, the bactericidal properties of several concentrations of ozone water were confirmed with Staphylococcus aureus and methicillin-resistant S. pseudintermedius. Both 3 and 11 mg/L of ozone water exhibited a significant bactericidal effect against staphylococci at less than 100 times dilution. We next examined the cellular cytotoxicity and cytokine production (Interleukin (IL)-6 and IL-8) induced by S. pseudintermedius pre-treated with ozone water, and our findings indicated that cytotoxicity and cytokine production induced by staphylococci were significantly inhibited after ozone water pre-treatment. In vivo experiments showed that ozone water-pre-treated S. pseudintermedius significantly inhibited the development of pyoderma in mice; however, limited effects were observed in a therapeutic setting. Interestingly, ozone water at concentrations of 3 and 11 mg/L exhibits dual bactericidal and anti-inflammatory effects in mice with AD. This observation was corroborated by the significant inhibition of cytokine production in interferon-γ/tumor necrosis factor-stimulated human epidermal keratinocyte cells exposed to ozone in vitro. These findings indicate that administering ozone can be a novel therapeutic approach for managing allergic skin diseases, such as AD.

Keywords: Atopic dermatitis; Keratinocyte; Ozone water; Pyoderma; Staphylococci.