Topical application of sustained released-carbon monoxide promotes cutaneous wound healing in diabetic mice. 2022

Tomohisa Takagi, and Tetsuya Okayama, and Jun Asai, and Katsura Mizushima, and Yasuko Hirai, and Kazuhiko Uchiyama, and Takeshi Ishikawa, and Yuji Naito, and Yoshito Itoh
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. Electronic address: takatomo@koto.kpu-m.ac.jp.

Clinical incidences of pressure ulcers in the elderly and intractable skin ulcers in diabetic patients are increasing because of the aging population and an increase in the number of diabetic patients worldwide. Although various agents are used to treat pressure and skin ulcers, these ulcers are often refractory and deteriorate the patients' quality of life. Therefore, a novel therapeutic agent with a novel mechanism of action is required. Carbon monoxide (CO) contributes to many physiological and pathophysiological processes, including anti-inflammatory activity; therefore, it can be a therapeutic gaseous molecule. Recent studies have revealed that CO accelerates wound healing in gastrointestinal tract injuries. However, it remains unclear whether CO promotes cutaneous wound healing. Therefore, we aimed to evaluate the therapeutic effects of topical application of a CO-containing solution and elucidate the underlying mechanism. A full-thickness skin wound generated on the back of diabetic mice was treated topically with CO or vehicle. Sustained release of CO was achieved using polyacrylic acid (PAA) as a thickener. The administration of CO-containing PAA aqueous solution resulted in a significant acceleration in wound recovery without elevating serum CO levels in association with increased angiogenesis and supported by elevated expression of vascular endothelial growth factor mRNA in the wound granulomatous tissues. These data suggest that CO might represent a novel therapeutic agent for the treatment of cutaneous wounds.

UI MeSH Term Description Entries
D011788 Quality of Life A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral, social environment as well as health and disease. HRQOL,Health-Related Quality Of Life,Life Quality,Health Related Quality Of Life
D002248 Carbon Monoxide Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed) Monoxide, Carbon
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000287 Administration, Topical The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example. Drug Administration, Topical,Administration, Topical Drug,Topical Administration,Topical Drug Administration,Administrations, Topical,Administrations, Topical Drug,Drug Administrations, Topical,Topical Administrations,Topical Drug Administrations
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D012883 Skin Ulcer An ULCER of the skin and underlying tissues. Skin Ulcers,Ulcer, Skin,Ulcers, Skin
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings

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