The Application of a Low-temperature Physical Plasma Device Operating Under Atmospheric Pressure Leads to the Production of Toxic NO₂

Abstract

Background: Physical plasma is a mixture of reactive particles and electromagnetic radiation. Due to the antimicrobial, immunomodulatory, anti-inflammatory, wound-healing promoting, and antineoplastic effects of body tempered physical plasma under atmospheric pressure (cold atmospheric plasma: CAP), CAP therapy is increasingly becoming the focus of surgical and oncological disciplines. However, when applied in practice, a potential emission of harmful noxae such as toxic nitrogen oxides must be taken into account, which was investigated in the following study. Materials and Methods: MiniJet-R Ar CAP device was characterized with respect to NO X -specific spectra, ultraviolet radiation C (UVC) intensity in the range of 200-275 nm and the formation of NO X gases. Instrument-specific parameters such as gas flow, energy setting of the highfrequency generator, and flow rate of the carrier gas Ar were varied. To test the toxic properties of the NO 2 concentrations formed by CAP, SK-OV-3 human ovarian cancer cells were incubated with different NO 2 concentrations and cell growth was monitored for 120 h. Results: The operation of MiniJet-R led to the formation of NO 2 in the proximity of the CAP effluent. Synthesis of NO led to a NO-specific spectrum in the range of 100-275 nm, whereby UVC radiation produced reached intensities of up to 90 mW/m 2 . NO gas itself, however, was not detectable, as it was converted to NO 2 rapidly. Cell culture incubation experiments demonstrated that NO 2 in these concentration ranges had no influence on the cell growth of human cancer cells. Conclusion: Although no limit values were exceeded in the present study, the emission of high-energy UVC radiation and toxic NO 2 is a risk factor with regard to the legal regulations on workplace protection (operator hazard) and the approval of medical devices (patient hazard). This is important for considerations regarding treatment frequency and duration. The growth inhibitory effect of CAP treatment on human cancer cells principally suggests a medical application of the MiniJet-R device, although more extensive studies will have to follow.Physical plasma is a mixture of particles of a carrier gas and ambient air with different ionization and excitation states, as well as electromagnetic radiation of different wavelengths including ultraviolet radiation C (UVC). In medical applications, body-tempered ('cold') plasmas up to about 40˚C under normal atmospheric pressure (cold atmospheric plasma: CAP) are utilized (1, 2). CAP has antimicrobial, immunomodulating, anti-inflammatory, wound-healing promoting, and antineoplastic effects on biological tissue and is therefore tested for its applicability in various medical fields. Due to the physical properties of CAP and against the 2591

Cold Atmospheric Plasma Promotes Regeneration-Associated Cell Functions of Murine Cementoblasts In Vitro

“…For EMD, as for pharmacological agents, a concentration can be defined, and dose-dependent effects can be detected [ 72 , 73 ]. In CAP treatment, it is not possible to define a concentration (of reactive species, for example) because these species continue to react very rapidly and have very short half-lives [ 74 ]. The only practical specification is the treatment duration, which leads to reproducible treatment duration-dependent effects [ 38 , 75 ].…”

New technologies for tissue replacement

“…No reported local or systemic side effects when the dose and timing of application (20-180" daily; 7-14 days of treatment) are respected. Despite the fact that one study demonstrates the production of ultraviolet light (UV) radiation and of NO2, and their dispersion in the environment is a consequence of CAP production, no pathologic sequelae were reported by the authors of the paper (18).…”

Impact of Non-Invasive Physical Plasma on Heat Shock Protein Functionality in Eukaryotic Cells

“…Expression levels of HSP40 and BAG3 were significantly enhanced [96,131], suggesting that NIPP exposure expands ROS levels inhibiting NIPP-induced apoptosis. Previous studies have shown that nitric oxide (NO) is produced during NIPP treatment and rapidly converted to other ROS, including NOX [132,133]. NO induces HSF1-regulated HSP70 expression and subsequent cytoprotection [125,126,134].…”