Abstract

The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology and dentistry, and it is considered a promising tool for cancer therapy. However, the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and there are no biological tools to determine the appropriate clinical dosages of Ar-PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to induce cell death in two-dimensional (2D) cell culture systems. By contrast, no detrimental effects of Ar-PJ were shown in our 3D zebrafish systems composed of 2D cells. The Ar-PJ-treated caudal fins grew by an average length of 0.7 mm, similar to the length of the normally regenerating fins. Remarkably, Ar-PJ did not affect the expression patterns of Wnt8a and β-Catenin, which play important roles in fin regeneration. In the embryo system, 85% of the Ar-PJ-treated embryos hatched, and the lateral length of these embryos was ~3.3 mm, which are equivalent to the lengths of normal embryos. In particular, vasculogenesis, which is the main cellular process during tissue regeneration and embryogenesis, occurred normally under the Ar-PJ dose used in this study. Therefore, our biosafety evaluation tools that use living model systems can be used to provide an experimental guideline to determine the clinically safe dosage of Ar-PJ.

Highlights

  • Nonthermal atmospheric argon (Ar) plasma has several distinct advantages that are applicable to medical use.[1,2] First, noble gases are safe for human use because they are typically highly unreactive

  • We investigated the effects of a jet-type of dielectric barrier discharge (DBD) Ar plasma (Ar-PJ) on 2D monolayer cells (Figure 2b)

  • Following 24 h of incubation, Mouse embryonic fibroblast (MEF) were stained with propidium iodide (PI), which is a red fluorescent dye that is impermeant to intact membranes in live cells but penetrates the damaged membranes of dead cells

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Summary

Introduction

Nonthermal atmospheric argon (Ar) plasma has several distinct advantages that are applicable to medical use.[1,2] First, noble gases are safe for human use because they are typically highly unreactive. The noble gas Ar is required to ensure the stability of plasma (Ar++e− → Ar). Ar is less expensive than other noble gases because it is the third most abundant gas in the Earth’s atmosphere, after nitrogen and oxygen. Ar plasma contains less ozone, which is harmful to living organisms, than do other gas plasmas.[3] Nonthermal Ar plasma has been demonstrated to be biocompatible because of its capacity to generate low-temperature, highly reactive species, including reactive oxygen species (ROS), and the easy control of its plasma dynamics.[4,5]

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