Carbonate Ion-Enriched Hot Spring Water Promotes Skin Wound Healing in Nude Rats

Abstract

Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

Diversity and enzymatic potential of thermophilic bacteria associated with terrestrial hot springs in Algeria

“…Moreover, it hosts Hammam Debagh, also named Hammam Challala that presents temperatures up to 98°C, which offers the hottest terrestrial spring in the country [20] and the second in the world after those of Iceland [21]. Algerian hot springs formerly were only used as spas for balneology [22], regarding their therapeutic effects [23]. At these spots, researchers were mainly interested in geothermal potential, physicochemical composition, and bacteriological and fungal contamination investigations to ensure the safety of users [24][25][26].…”

Intra-arterially infused carbon dioxide-saturated solution for sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model

“…Cleaved caspase-3 and cleaved caspase-9 are activated forms of caspase-3 and caspase-9, and are commonly used to detect apoptosis (22). HIF-1α is a basic helix-loop-helix-PAS (bHLH-PAS) transcription factor that has an essential role in O 2 homeostasis (6,7,9,10), and has recently emerged as a major factor influencing tumor proliferation and malignant progression (23,24). Hypercapnia was reported to counter-regulate the activation of the HIF pathway by reducing the intracellular pH (25).…”

“…Tumor hypoxia is a potential therapeutic problem because of its adverse impact on the effectiveness of chemotherapy. Carbon dioxide (CO 2 ) therapy has historically been used for its therapeutic effect on skin problems (4)(5)(6). The mechanisms of this beneficial effect are an increase in blood flow and microcirculation, nitric oxidedependent neocapillary formation, and a partial increase in oxygen pressure in the local tissue, known as the Bohr effect (7).…”

Bioinorganics and Wound Healing

“…Often associated with calcium (under CaCO 3 form), the direct effects of carbonates are rarely investigated but utilization of carbonate salts (discussed previously) has resulted in interesting positive results on wound closure, or as hemostatic agents . Carbonate‐enriched hot water has been demonstrated to significantly improve wound closure; however, the influence of the other ions potentially beneficial to the healing (e.g.,: calcium) was not studied. Local delivery of carbon dioxide releasing microparticles has been shown to improve blood flow, wound closure, as well as microvessel formation and collagen deposition …”