Reactive oxygen species (ROS) and the closely related reactive nitrogen species (RNS) are often generated in applications of atmospheric pressure plasmas intended for biomedical purposes. These species are also central players in what is sometimes referred to as ‘redox’ or oxidation‐reduction biology. Oxidation‐reduction biochemistry is fundamental to all of aerobic biology. ROS and RNS are perhaps best known as disease-associated agents, implicated in diabetes, cancer, heart and lung disease, autoimmune disease and a host of other maladies including ageing and various infectious diseases. These species are also known to play active roles in the immune systems of both animals and plants and are key signalling molecules, among many other important roles. Indeed, the latest research has shown that ROS/RNS play a much more complex and nuanced role in health and ageing than previously thought. Some of the most potentially profound therapeutic roles played by ROS and RNS in various medical interventions have emerged only in the last several years. Recent research suggests that ROS/RNS are significant and perhaps even central actors in the actions of antimicrobial and anti-parasite drugs, cancer therapies, wound healing therapies and therapies involving the cardiovascular system. Understanding the ways ROS/RNS act in established therapies may help guide future efforts in exploiting novel plasma medical therapies. The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but these species are just as important in plants. It appears that there are opportunities for useful applications of plasmas in this area as well. (Some figures may appear in colour only in the online journal)

https://iopscience.iop.org/article/10.1088/0022-3727/45/26/263001/pdf

The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology

The formation of transient species (OH?, NO2?, NO radicals) and long-lived chemical products (O3, H2O2, , ) produced by a gas discharge plasma at the gas?liquid interface and directly in the liquid was measured in dependence on the gas atmosphere (20% oxygen mixtures with nitrogen or with argon) and pH of plasma-treated water (controlled by buffers at pH 3.3, 6.9 or 10.1). The aqueous-phase chemistry and specific contributions of these species to the chemical and biocidal effects of air discharge plasma in water were evaluated using phenol as a chemical probe and bacteria Escherichia coli. The nitrated and nitrosylated products of phenol (4-nitrophenol, 2-nitrophenol, 4-nitrocatechol, 4-nitrosophenol) in addition to the hydroxylated products (catechol, hydroquinone, 1,4-benzoquinone, hydroxy-1,4-benzoquinone) evidenced formation of NO2?, NO? and OH? radicals and NO+ ions directly by the air plasma at the gas?liquid interface and through post-discharge processes in plasma-activated water (PAW) mediated by peroxynitrite (ONOOH). Kinetic study of post-discharge evolution of H2O2 and in PAW has demonstrated excellent fit with the pseudo-second-order reaction between H2O2 and . The third-order rate constant k?=?1.1???103?M?2?s?1 for the reaction was determined in PAW at pH 3.3 with the rate of ONOOH formation in the range 10?8?10?9?M?s?1. Peroxynitrite chemistry was shown to significantly participate in the antibacterial properties of PAW. Ozone presence in PAW was proved indirectly by pH-dependent degradation of phenol and detection of cis,cis-muconic acid, but contribution of ozone to the inactivation of bacteria by the air plasma was negligible.

https://iopscience.iop.org/article/10.1088/0963-0252/23/1/015019/pdf

Aqueous-phase chemistry and bactericidal effects from an air discharge plasma in contact with water: evidence for the formation of peroxynitrite through a pseudo-second-order post-discharge reaction of H 2 O 2 and HNO 2

Reactive species in non-equilibrium atmospheric-pressure plasmas: Generation, transport, and biological effects

Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics and nonpharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma, and medicinal honey. A brief final section covers reactive nitrogen species and related therapeutics, such as acidified nitrite and nitric oxide-releasing nanoparticles.

Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

Plasmas for medicine

This introductory review on plasma health care is intended to provide the interested reader with a summary of the current status of this emerging field, its scope, and its broad interdisciplinary approach, ranging from plasma physics, chemistry and technology, to microbiology, biochemistry, biophysics, medicine and hygiene. Apart from the basic plasma processes and the restrictions and requirements set by international health standards, the review focuses on plasma interaction with prokaryotic cells (bacteria), eukaryotic cells (mammalian cells), cell membranes, DNA etc. In so doing, some of the unfamiliar terminology—an unavoidable by-product of interdisciplinary research—is covered and explained. Plasma health care may provide a fast and efficient new path for effective hospital (and other public buildings) hygiene— helping to prevent and contain diseases that are continuously gaining ground as resistance of pathogens to antibiotics grows. The delivery of medically active 'substances' at the molecular or ionic level is another exciting topic of research through effects on cell walls (permeabilization), cell excitation (paracrine action) and the introduction of reactive species into cell cytoplasm. Electric fields, charging of surfaces, current flows etc can also affect tissue in a controlled way. The field is young and hopes are high. It is fitting to cover the beginnings in New Journal of Physics, since it is the physics (and non- equilibrium chemistry) of room temperature atmospheric pressure plasmas that have made this development of plasma health care possible.

/pdf/plasma-medicine-an-introductory-review-16ncxlrbef.pdf

Plasma medicine: an introductory review

The recent tremendous progress in understanding physical plasma phenomenon, together with the development of new plasma sources has put growing focus on the application of plasmas in health care. Active plasma components, such as molecules, atoms, ions, electrons and photons, reactive species, ultraviolet radiation, optical and infrared emission and heat have the ability of activating, controlling and catalysing reactions and complex biochemical procedures. Thermal and non-thermal (i.e. cold) plasmas - both already widely established in medicine - are used for various therapeutic applications. Particularly in dermatology, plasma applications hold big potential, for example, in wound healing, such as efficient disinfection or sterilization, therapy of various skin infections or tissue regeneration. This review gives an overview on potential plasma applications in medicine - including the recent research on skin diseases - and summarizes possible interactions between plasmas and living tissue.

Tetyana Nosenko

Papers

Plasma medicine: an introductory review

Plasma applications in medicine with a special focus on dermatology

Characterization of Low‐Temperature Microwave Plasma Treatment With and Without UV Light for Disinfection

Low-temperature Argon plasma - a new strategy against multiresistance of germs and impaired wound healing

Low-temperature atmospheric-pressure plasmas as a source of reactive oxygen and nitrogen species for chronic wound disinfection