The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis‐resistance to non‐thermal plasma therapy

Abstract

Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestosinduced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.

Novel Intraperitoneal Treatment With Non-Thermal Plasma-Activated Medium Inhibits Metastatic Potential of Ovarian Cancer Cells

“…The associations of PAM with these cellular factors and pathways remain unclear. Plasma consists of highly reactive components, including electrons, ions, radicals and UV, and it interacts with surrounding molecules such as moisture and oxygen and nitrogen in air, resulting in secondary highly reactive components 46 . Based on many plasma studies, it is well known that the biological effects of PAM are responsible for ROS/RNS species such as H 2 O 2 , NO 2 − and NO 3 − , generated by reactive species in a gas phase and liquid phase and a direct interaction of plasma with liquid.…”

Renal tumors in end‐stage renal disease: A comprehensive review

“…What causes RCC in ESRD patients is difficult to determine owing to the presence of numerous carcinogenic factors in these patients. Oxidative stress is thought to promote carcinogenesis in various organs, including the kidneys . It has been shown to cause mitochondrial DNA mutations and DNA hypermethylation in RCCs in ESRD patients .…”

State of the art in medical applications using non-thermal atmospheric pressure plasma

“…Non-thermal atmospheric pressure plasma and PAM generally induce intracellular ROS such as superoxide, hydrogen peroxide, and hydroxyl radical in cells, thus inducing apoptosis (Ahn et al 2011;Sensenig et al 2011;Graves 2012;Joh et al 2012;Tanaka et al 2015b;Toyokuni 2016).…”

“…This protective effect may be due, in part, to the transport of Lascorbate into cells, where it has an anti-oxidant effect Fig. 82 Generation of ROS (Toyokuni 2016). ÁOH (hydroxyl radical), 1 O 2 (singlet oxygen), and ONOO -(peroxynitrite) are the most reactive chemical species in the biological system.…”

“…82, (Toyokuni 2016)]. Superoxide is converted into hydrogen peroxide by superoxide dismutase (SOD), hydrogen peroxide is converted into hydroxyl radical by Fenton reaction, and catalase catalyzes the breakdown of hydrogen peroxide into water and oxygen.…”