Administration Of Hydrogen Peroxide Research Articles

Functional inactivation of the oestrogen receptor by the antioestrogen, ZM 182780, sensitises tumour cells to reactive oxygen species.

Reactive oxygen species (ROS) play a fundamental role in both apoptotic and necrotic cell death. Their importance is highlighted by studies showing that they mediate cell death in response to radiotherapy and to some forms of chemotherapy. Here we provide the first evidence for a role of ROS in response to an antiendocrine agent currently undergoing clinical trials. Using the oestrogen receptor (ER) containing rat pituitary GH3 cell line, we show that cell death is induced by the pure steroidal antioestrogen, ZM 182780, and that this is blocked by the antioxidant, N-acetyl cysteine (NAC). By flow cytometry, we show that, prior to the onset of DNA breakdown measured by ELISA, ZM 182780 exposure has no significant effect on intracellular oxidant concentrations. In contrast, ZM 182780 exposure greatly increases sensitivity to oxidants generated by blocking cellular antioxidant pathways and from exogenous administration of hydrogen peroxide (H2O2). As both necrosis and apoptosis are controlled by mitochondrial function, further experiments conducted to determine mitochondrial membrane potential (Delta|gWm) have indicated that the ZM 182780-induced loss of ER function increases the ease with which oxidants collapse mitochondrial activity and, as a consequence, cell death.

Peroxide treatment changes activity of non specific esterase in vascular endothelium of isolated pig aorta in vitro

The effect of hydrogen peroxide on certain enzymes contained in endothelial cells was investigated in vitro. Specifically in this study the influence of hydrogen peroxide on the non-specific esterase activity in endothelial cells of the perfused pig aorta was examined. We perfused an isolated segment of the pig aorta for 10 h and added 5, 10, 12, 15 ml 10% hydrogen peroxide to 100 ml perfused medium. In unperfused pig aorta 99.34% of the endothelial cells reacted positive. After 10 h of perfusion without hydrogen peroxide administration 93.25% endothelial cells still showed positive enzyme reactivity. In presence of hydrogen peroxide in the perfusion medium the activity of non-specific esterase was progressively inhibited, finally causing complete inactivation.

Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents.

The study examined the potentiation of the antinociceptive action of opioid analgesics produced by gaseous superoxide (GS) in the rat hind paw withdrawal test (PWT) and by GS or hydrogen peroxide (HP) in the formalin test. In the PWT, inhalation of GS for 50 minutes before i.p. injection of threshold doses of morphine (0.5 mg/kg) and trimeperidine (1.0 mg/kg) increased the threshold of nociception (TN) by a maximum of 43.0% (p < 0.05) and 113.4% (p < 0.01) respectively. The GS/trimeperidine-dependent increase in TN showed two peaks, the second of which could be suppressed by nialamide. Naloxone abolished the GS/ morphine-dependent increased in the TN. In the formalin test, a significant antinociceptive effect developed after GS inhalation or HP administration (intranasally, 2 x 5 microliters of 2 x 10(-5) mol/l solution in saline) in combination with low doses of Omnopon (0.06-0.75 mg/kg). These results suggest that both GS and HP potentiate the antinociceptive effects of opioid analgesics.

Risques de l'irrigation au peroxyde d'hydrogène en chirurgie de guerre

Two cases of severe complications due to injection of hydrogen peroxide under pressure into areas of muscular attrition in war wounds are reported. In both cases the administration of hydrogen peroxide was associated with tachypnoea, with major arterial desaturation and a precordial « mill-wheelmurmur was heard. In one case, these symptoms were followed by hemiplegia caused by paradoxical arterial gas embolism, and in the other case by a pulmonary oedema confirmed by computerized tomography. Both patients recovered under hyperbaric oxygen therapy. The release of gaseous oxygen under the effect of tissue catalase and the membrane peroxydasic activity of hydrogen peroxide initiate such complications. The injection of hydrogen peroxide under pressure into a closed or partially closed cavity should therefore be strictly prohibited.

Catalase protection against hydrogen peroxide-induced injury in rat oral mucosa

Hydrogen peroxide in contact with the oral mucosa induces vesicle formation and ulceration. This study assesses the protective effect of catalase against the hydrogen peroxide insult in the rat tongue mucosa. In addition, we report a detailed histologic characterization of the mucosal injury. Four repetitive applications of 30% hydrogen peroxide at 15 minute intervals produced a vast edema of the submucosal tissue including the tongue muscles that was seen immediately after the last application. Histomorphometric measurements indicated a substantial regression of the edema 1 day later with the appearance of a very large ulceration lined by a pyogenic membrane. Animals examined 7 days after the hydrogen peroxide administration revealed almost complete healing in terms of absence of edema and renewal of intact epithelial lining. Catalase applied to the tongue before the hydrogen peroxide fully prevented the pathologic tissue reaction. Thus testing of the clinical feasibility of catalase in protecting the oral mucosa against hydrogen peroxide-induced injury is strongly indicated.

Diffusion coefficient for O 2 in plasma and mitochondrial membranes of rat cardiomyocytes

Oxygen diffusion in plasma membranes and mitochondrial (Mt) membranes of ventricular myocytes isolated from adult rat hearts was measured using O 2-induced fluorescence quenching of pyrenebutyric acid. The diffusion coefficient for oxygen (D O 2 in 10 −6·cm 2·s −1) of the plasma membrane was 2.91 ± 0.05 (37°C) in the control group, which was significantly higher than that of Mt membrane (2.23 ± 0.11) ( P < 0.001). The D O 2 of the plasma membrane was reduced to 2.50 ± 0.08 ( P < 0.001) in myocytes isolated from heart after 15 min reperfusion following no-flow ischemia for 30 min, while that of the Mt membrane remained almost unchanged. Administration of hydrogen peroxide and hypochlorous acid to the isolated myocytes also reduced the plasma membrane D O 2 . The decrease in the plasma membrane D O 2 correlated with that in the fraction of rod-shaped myocytes. We conclude that the plasma membrane is more susceptible to reperfusion injury than the Mt membrane, but these membranes do not limit O 2 uptake in the heart because of the high absolute values of D O 2 .

Hydroperoxide-Induced Broncho- and Vasoconstriction in the Isolated Rat Lung

The effects of different hydroperoxides on lung mechanics and perfusate flow rate and their mechanisms of action were studied in isolated perfused rat lungs. The administration of hydrogen peroxide, t-butyl hydroperoxide, cumene hydroperoxide, linoleic acid hydroperoxide, and linoleic acid ethylester hydroperoxide (0.1-2 mM) to the perfusate caused a marked decrease in lung compliance, conductance, and perfusate flow rate, with constriction strength of t-butyl hydroperoxide greater than hydrogen peroxide greater than cumene hydroperoxide greater than linoleic acid ethylester hydroperoxide greater than linoleic acid hydroperoxide. Although the hydroperoxides probably had to enter lung cells to exert their effects, no relationship was found between constriction strength and amount of hydroperoxide taken up by the lung. Reduced sensitivity was apparent after repeated dosing, depending on the length of time between dosing. The addition of the iron chelator Desferal (1 mM) had no effect on the hydroperoxide-induced broncho- and vasoconstriction, although free iron was reduced by 50% in the lungs. The administration of the antioxidants diphenyl-p-phenylenediamine (50 microM) or butylated hydroxyanisole (200 microM) to the perfusate 20 min prior to the hydroperoxide attenuated the hydroperoxide-induced effects as well as arachidonic acid-induced broncho- and vasoconstriction. Our findings have shown that hydroperoxides that can enter the lung cells will also induce both vaso- and bronchoconstriction in the isolated perfused rat lung.

Effect of hydrogen peroxide administration on life span, superoxide dismutase, catalase, and glutathione in the adult housefly, Musca domestica

The general objective of this study was to further elucidate the relationship between oxidative stress and the aging process. H 2O 2 is known to be a progenator of reactive oxygen species, such as hydroxyl free radical, by various mechanisms involving, among others, a superoxide anion radical-driven Fenton cycle, or splitting of the 0−0 bond by hemoproteins. Effects of H 2O 2 administration on life span, activities of superoxide dismutase, catalase, concentrations of endogenous H 2O 2, and glutathione in the housefly are described. Adult male flies were given various concentrations of H 2O 2, ranging from 0 to 100 mM H 2O 2, in their drinking water. Life span was shortened by H 2O 2 intake except in 10 mM H 2O 2 administrated flies, which exhibited the longest life span. Flies administered mM H 2O 2 also contained the highest concentration of reduced glutathione (GSH). Superoxide dismutase and catalase activities were not affected by H 2O 2 intake. Compensatory elevation in GSH may be responsible for the increase in life span observed in 10 mM H 2O 2 administered flies.

Lack of antibacterial activity after intravenous hydrogen peroxide infusion in experimental Escherichia coli sepsis

The intravenous administration of hydrogen peroxide has been reported to benefit patients with pneumonia and to reduce Plasmodium parasitemia in experimentally infected mice. We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits. No decrease in the level of bacteremia was detected at the maximum intravenous infusion rate of hydrogen peroxide physiologically tolerated by the rabbits (2.0 mumol/h). Moreover, the addition ex vivo of greater amounts of hydrogen peroxide to human or murine blood containing E. coli resulted in no detectable antibacterial action. In contrast, ethyl hydrogen peroxide, which is not affected by catalase, was bactericidal when added ex vivo to human blood containing E. coli. These results suggest that extracellular hydrogen peroxide, whether of exogenous or endogenous origin, does not have antibacterial activity in the blood of animals having even low levels of catalase.

Skeletal muscle function in hypoxia: Effect of alteration of intracellular myoglobin

Enhancement of oxygen flux through myoglobin containing solutions due to myoglobin facilitated oxygen diffusion is well recognized and is most apparent under conditions of hypoxia. To examine the function of intracellular myoglobin in vivo under conditions of hypoxia, the in situ dog gastrocnemius-plantaris musclle was studied. Administration of 10% oxygen resulted in arterial P O 2 values between 32 and 36 mm Hg. Muscle oxygen consumption and isometric tension generation were determined during sustained 3-Hz contractions before and after administration of hydrogen peroxide that converted functional myoglobin to forms incapable of reversible combination with oxygen. Muscle blood flow, perfusion pressure, and muscle oxygen delivery were unchanged by such treatment. Hydrogen peroxide administration resulted in oxidation of intracellular myoglobin with a resultant decrease of 37% in muscle oxygen consumption and 42% in tension generation after 20 min of stimulation. In a control group not receiving hydrogen peroxide muscle oxygen consumption and tension generation decreased by 13% and 12%, respectively. We conclude that intact functional myoglobin is important in maintaining muscle function in isometric exercise under conditions of hypoxia.

Failure to Achieve Oxygen Supplementation with Hydrogen Peroxide

Hydrogen peroxide, administered rectally or intraperitoneally, has been reported to improve systemic oxygenation. Therefore, the effectiveness of intraperitoneal administration of hydrogen peroxide, 0.3%, was investigated in hypoxic rabbits as a possible method of supplementation of oxygenation in respiratory distress syndrome or in the postoperative cardiac patient. Although hydrogen peroxide initially caused a slight increase in arterial oxygen saturation, this increase was brief and was followed by a marked fall in arterial oxygen saturation. Hypotension occurred in all rabbits. It is suggested that the intraperitoneal administration of hydrogen peroxide for the purpose of extrapulmonary oxygenation is largely ineffective and hazardous, and it probably should not be attempted in the human subject.

STUDIES ON THE PARENTERAL ADMINISTRATION OF HYDROGEN PEROXIDE

STUDIES ON THE PARENTERAL ADMINISTRATION OF HYDROGEN PEROXIDE