Water from Nitrodi’s Spring Induces Dermal Fibroblast and Keratinocyte Activation, Thus Promoting Wound Repair in the Skin: An In Vitro Study

Abstract

The Romans knew of Nitrodi’s spring on the island of Ischia more than 2000 years ago. Although the health benefits attributed to Nitrodi’s water are numerous, the underlying mechanisms are still not understood. In this study, we aim to analyze the physicochemical properties and biological effects of Nitrodi’s water on human dermal fibroblasts to determine whether the water exerts in vitro effects that could be relevant to skin wound healing. The results obtained from the study indicate that Nitrodi’s water exerts strong promotional effects on dermal fibroblast viability and a significant stimulatory activity on cell migration. Nitrodi’s water induces alpha-SMA expression in dermal fibroblasts, thus promoting their transition to myofibroblast-protein ECM deposition. Furthermore, Nitrodi’s water reduces intracellular reactive oxygen species (ROS), which play an important role in human skin aging and dermal damage. Unsurprisingly, Nitrodi’s water has significant stimulatory effects on the cell proliferation of epidermal keratinocytes and inhibits the basal ROS production but enhances their response to the oxidative stress caused by external stimuli. Our results will contribute to the development of human clinical trials and further in vitro studies to identify inorganic and/or organic compounds responsible for pharmacological effects.

Calcinosis Cutis and Calciphylaxis in Autoimmune Connective Tissue Diseases

“…SSc is a complex autoimmune connective tissue disease affecting the skin, gastrointestinal tract, and lungs, which carries potentially life-threatening complications [ 18 , 19 ]. Microvascular changes with endothelial cell dysfunction, followed by their transition into myofibroblasts, are central in the pathogenesis of the disease [ 20 , 21 ]. In addition, the development of progressive fibrosis and ischemia involving skin and other organs may lead to their irreversible failure [ 22 ].…”

The Benefits of Water from Nitrodi’s Spring: The In Vitro Studies Leading the Potential Clinical Applications

“…3509, 9 October 2003). Our group recently undertook an experimental project on Nitrodi’s water wherein additional chemical and chemical–physical analyses were performed [ 41 ], the main results of which are reported in Table 1 .…”

“…Regarding its clinical use, it is considered a bicarbonated water, although it does not completely meet the European Union’s requisites for such natural mineral water. It is also alkaline-earthy and naturally hypothermal [ 29 , 33 , 41 , 42 , 43 ]. Our analysis of its physical and chemical composition allows us to speculate on the beneficial properties of Nitrodi’s water.…”

“…The richness of the bicarbonate and the mixture of minerals contained in Nitrodi’s water favor natural skin exfoliation, i.e., peeling, thus removing damaged and aged skin [ 47 ]. Exfoliation induces keratinocyte and fibroblast migration, structural reorganization, and the deposition of new collagen, which are all effects induced by Nitrodi’s water [ 41 ].…”

“…Recent evidence has shown that oxidative stress plays a pivotal role in the development and perpetuation of inflammation [ 62 ]. Oxidative stress implies increased intracellular ROS levels, which are involved in both chronological aging and photo-aging [ 41 ]. Promising results have been obtained from using natural antioxidant compounds as pharmaceutical tools against several inflammatory diseases in in vitro systems, in vivo models, and in clinical trials.…”