Proteomic analysis of mitochondrial proteins in the guinea pig heart following long-term normobaric hyperoxia.

Normobaric hyperoxia is applied for the treatment of a wide variety of diseases and clinical conditions related to ischemia or hypoxia, but it can increase the risk of tissue damage and its efficiency is controversial. In the present study, we analyzed cardiac mitochondrial proteome derived from guinea pigs after 60 h exposure to 100% molecular oxygen (NBO) or O2 enriched with oxygen cation (NBO+). Two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry identified twenty-two different proteins (among them ten nonmitochondrial) that were overexpressed in NBO and/or NBO+ group. Identified proteins were mainly involved in cellular energy metabolism (tricarboxylic acid cycle, oxidative phosphorylation, glycolysis), cardioprotection against stress, control of mitochondrial function, muscle contraction, and oxygen transport. These findings support the viewpoint that hyperoxia is associated with cellular stress and suggest complex adaptive responses which probably contribute to maintain or improve intracellular ATP levels and contractile function of cardiomyocytes. In addition, the results suggest that hyperoxia-induced cellular stress may be partially attenuated by utilization of NBO+ treatment.

Effect of normobaric oxygen treatment on oxidative stress and enzyme activities in guinea pig heart.

Normobaric oxygen (NBO) therapy is commonly applied for the treatment of various diseases, including myocardial infarctions, but its effectiveness is controversial. Potential adverse effects of hyperoxia are related to excessive formation of free radicals. In the present study we examined the effect of 60-h NBO treatment on lipid peroxidation (LPO), activity of manganese superoxide dismutase (Mn-SOD) and mitochondrial enzymes of energy metabolism in guinea pig heart. NBO treatment resulted in significant accumulation of thiobarbituric acid reactive substances and loss of Mn-SOD activity despite slight elevation of Mn-SOD protein content. Activity of electron transport chain complex III decreased significantly, while activity of complex IV was slightly elevated and citrate synthase was unchanged. LPO, inhibition of Mn-SOD and complex III activities were more pronounced when inhaled oxygen was partially enriched with superoxide radical. In contrast, when O(2) was enriched with oxygen cation (O(2)●+), LPO and loss of Mn-SOD activity were prevented. Complex III activity in the O(2)●+-treated group remained depressed but activities of complex IV and citrate synthase were elevated. These data suggest that NBO treatment is associated with myocardial oxidative damage and attenuation of antioxidant defense, but these adverse effects can be partially attenuated by inhalation of O(2) enriched with oxygen cation.

Effect of long-term normobaric hyperoxia on oxidative stress in mitochondria of the guinea pig brain.

Normobaric hyperoxia (NBO) is applied for treatment of various clinical conditions related to hypoxia, but it can potentially also induce generation of reactive oxygen species, causing cellular damage. In this study, we examined the effects of 60 h NBO treatment on lipid and protein oxidative damage and activity of superoxide dismutase (Mn-SOD) in brain mitochondria of guinea pigs. Despite significant stimulation of Mn-SOD expression and activity the NBO treatment resulted in accumulation of markers of oxidative lesions, including lipid peroxidation (conjugated dienes, thiobarbituric acid reactive substances) and protein modification (bityrosines, adducts with lipid peroxidation products, oxidized thiols). When inhaled O(2) was enriched with oxygen cation, O (2) (•+) , the Mn-SOD expression and activity were stimulated to similar extend, but lipid peroxidation and protein oxidation were prevented. These results suggest that long-term NBO treatment causes oxidative stress, but enrichment of inhaled oxygen by oxygen cation can protect the brain again adverse effects of hyperoxia.

Reactive oxygen species, especially O2+* in cancer mechanisms.

UNLABELLED: In the nature including the human organism there are 5 reactive oxygen species (ROS): O2, O2-*, O2+*, 1O2, O3 with different electromagnetic characteristics and biological effects. The effects of enrichment of medical oxygen O2 with traces of ROS on various cells were tested in experiments. METHODS: Human embryonic lung fibroblasts WI38 damaged by Radon Rn222 into WI38/ Rn cells and WI38 cells transformed by virus SV40 into VA13 cells were exposed to different ROS gas mixtures, prepared in high - voltage plasma chamber of "Oxygen Ion 3000". Trans-membrane resting potential (TMRP) was measured and cells morphology was visually observed using microscopy during 10 days. RESULTS: Exposition of WI38, WI38/Rn and VA13 to medical O2, alone show no effect in TMRP and in cell morphology. But pico-concentration of O2+* in medical O2 increased the TMRP in WI38/Rn cells from -25mV to -35mV (variance 0.5-2mV) (p < 0.001) with improvement of cells morphology and the TMRP of VA13 cells from -15mV to -32mV (2-3mV) (p < 0.001) with a maximum effect on the 5th day. Later the TMRP strongly decreased and the cell membrane ruptured due to water influx. O2, enriched with O2-* alone or together with O2+* had no significant effect in WI38/Rn and VA13 groups (p > 0.05). CONCLUSION: Radon protective effect on WI38/Rn or destructive effect on VA13 of pico-concentrations of O2+* in medical O2 conforms to the theory of hormesis resp. to hypothesis of cancer induction mechanisms, supporting it's further experimental or clinical use.

Effects of partially ionised medical oxygen, especially with O2•-, in vibration white finger patients.

A major symptom of hand-arm vibration syndrome is a secondary Raynaud's phenomenon-vibration white finger (VWF)-which results from a vasospasm of the digital arteries caused by work with vibration devices leading to occupational disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The aim of this work was to verify the influence of inhalation of partially ionized oxygen (O2•-) on peripheral blood vessels in the hands of patients with VWF. Ninety one (91)patients with VWF underwent four-finger adsorption plethysmography, and the pulse wave amplitude was recorded expressed in numeric parameters-called the native record. Next, a cold water test was conducted following with second plethysmography. The patients were divided in to the three groups. First and second inhaled 20-min of ionized oxygen O2•- or oxygen O2 respectively. Thirth group was control without treatment. All three groups a follow-up third plethysmography-the post-therapy record. Changes in the pulse wave amplitudes were evaluated. Inpatients group inhaling O2•- a modest increase of pulse wave amplitude was observed compared to the native record; patients inhaling medical oxygen O2 and the control showed a undesirable decline of pulse wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the group inhaling O2•- compare to O2 (p < 0.05). Peripheral vasodilatation achieved by inhalation of O2•- could be used for VWF treatment without undesirable side effect in hospital as well as at home environment.