Oxygen, Volume 4, Issue 4 (December 2024) – 6 articles

Alterations in cellular energy metabolism are a hallmark of cancer and lactate dehydrogenase (LDH) enzymes are overexpressed in many cancers regardless of sufficient oxygen and functional mitochondria. Further, L-lactate plays signaling roles in multiple cell types. We evaluated the effect of singlet oxygen and hypochlorous acid (HOCl) on pig heart LDH-B, which shares 97% homology with human LDH-B. Singlet oxygen was generated photochemically using methylene blue or the chlorophyll metabolites, pheophorbide A and chlorin e6. Singlet oxygen induced protein crosslinks observed by SDS-PAGE under reducing conditions and inhibited LDH-B activity. Ascorbate, hydrocaffeic acid, glutathione and sodium azide were employed as singlet oxygen scavengers and shown to protect LDH-B. Using fluorescein-modified maleimide, no changes in cysteine availability as a result of singlet oxygen damage were observed. This was in contrast to HOCl, which induced the formation of disulfides between LDH-B subunits, thereby decreasing LDH-B labeling with fluorescein. HOCl oxidation inhibited LDH-B activity; however, disulfide reduction did not restore it. LDH-B cysteines were resistant to millimolar H₂O₂, chloramines and Angeli’s salt. In the absence of pyruvate, LDH-B enhanced NADH oxidation in a chain reaction initiated by singlet oxygen that resulted in H₂O₂ formation. Once damaged by either singlet oxygen or HOCl, NADH oxidation by LDH-B was impaired. Full article

Noble gases are a valuable but overlooked source of effective and safe therapeutics. Being monoatomic and chemically inert, they nonetheless have a surprisingly wide range of biochemical and medically valuable properties. This mini review briefly summarizes these properties for the most widely used noble gases and focuses and research gaps and missed opportunities for wider use of these intriguing ‘atomic’ drugs. The main research gaps and opportunities lie firstly in the application of advanced computational modelling methods for noble gases and recent developments in accurate predictions of protein structures from sequence (AlphaFold), and secondly in the use of very efficient and selective drug delivery technologies to improve the solubility, efficacy, and delivery of noble gases to key targets, especially for the lighter, poorly soluble gases. Full article

Bacteria-related infections remain a leading cause of dental implant failures. Despite the successful history of titanium implants, naturally forming oxides lack antibacterial properties. Crystalline oxides, modified through anodization processes, have shown photocatalytic-induced antibacterial properties when exposed to sufficient energy sources such as UVA light. Chemically doping these oxides with some metallic and non-metallic elements has been shown to enhance their photocatalytic activity (PCA). The present study’s objectives were to assess the relative UVA and violet-light-irradiated PCA levels, bacterial attachment levels, and pre-osteoblast early cell viability levels of phosphorus-doped and phosphorus-and-silver-doped anatase-phase oxides. Each oxide revealed similar surface topographies and surface porosity levels. However, the phosphorus-and-silver-doped oxides exhibited significantly higher PCA levels compared to the phosphorus-doped oxide counterpart after irradiation with 365 nm UVA (p < 0.0001) or 410 nm violet (p = 0.007 and 0.03) light. The phosphorus-doped oxides and phosphorus-and-silver-doped oxides revealed similar Staphylococcus aureus attachment levels after 60 min of UVA irradiation. The phosphorus-and-silver-doped oxides exhibited significantly increased 7-day cell viability compared to their phosphorus-doped oxide counterparts. Thus, it was concluded that the silver doping additions to the oxides show much promise for biomaterials applications and warrant further exploration. Full article

The diffusional dynamics and vibrational spectroscopy of molecular hydrogen (H₂) in myoglobin (Mb) is characterized. Hydrogen has been implicated in a number of physiologically relevant processes, including cellular aging or inflammation. Here, the internal diffusion through the protein matrix was characterized, and the vibrational spectroscopy was investigated using conventional empirical energy functions and improved models able to describe higher-order electrostatic moments of the ligand. Depending on the energy function used, H₂ can occupy the same internal defects as already found for Xe or CO (Xe1 to Xe4 and B-state). Furthermore, four additional sites were found, some of which had been discovered in earlier simulation studies. Simulations using a model based on a Morse oscillator and distributed charges to correctly describe the molecular quadrupole moment of H₂ indicate that the vibrational spectroscopy of the ligand depends on the docking site it occupies. This is consistent with the findings for CO in Mb from experiments and simulations. For H₂, the maxima of the absorption spectra cover ∼20 cm⁻¹ which are indicative of a pronounced Stark effect of the surrounding protein matrix on the vibrational spectroscopy of the ligand. Electronic structure calculations show that H₂ forms a stable complex with the heme iron (stabilized by ∼−12 kcal/mol), but splitting of H₂ is unlikely due to a high activation energy (∼50 kcal/mol). Full article

Skin grafting is a critical procedure for treating skin defects from burns, trauma, and surgical interventions, yet complications such as ischemia, necrosis, and infection can limit graft success. Hyperbaric Oxygen Therapy (HBOT) has emerged as a promising adjunctive treatment that enhances skin graft viability through mechanisms including enhanced oxygenation, angiogenesis, reduced inflammation, and anti-infective effects. This review synthesizes findings from clinical studies, comparative analyses, and case reports to clarify HBOT’s efficacy in improving skin graft outcomes. Methods include a comprehensive analysis of HBOT’s impact on graft take rates, healing times, and complication rates. Results indicate that HBOT significantly improves graft survival by mitigating ischemia and infection, while comparative studies show a reduction in major amputations and improved healing in complex cases, such as diabetic foot ulcers and traumatic injuries. These findings suggest that HBOT can serve as a valuable adjunct to standard grafting procedures, offering a multifaceted approach to improve graft viability, especially in high-risk cases. This review highlights HBOT’s potential for integration into wound management protocols, providing a foundation for further exploration into its efficacy and applications in reconstructive surgery. Full article

The success of heated tobacco products (HTPs) and electronic cigarettes (e-cigs) has been largely attributed to their ability to mimic the gestural experience of traditional cigarette smoking, while being perceived as a safer alternative due to the absence of combustion, as well as to their appeal, particularly among younger populations. Despite the initial idea that these new devices were harmless, recent literature reveals a concerning expanding body of evidence on their potential toxicity. Thus, this literature review aims to elucidate the mechanisms by which reactive oxygen species generated by HTPs and e-cigs induce oxidative stress and inflammation and the subsequent biological and health consequences, in order to raise awareness on the significance of addressing the potential toxicological effects associated with these devices, which are commonly believed to be safe. Full article