[Show abstract][Hide abstract] ABSTRACT: Since inflammation and oxidative stress are fundamental in the pathophysiology of neonatal meconium aspiration syndrome (MAS), various anti-inflammatory drugs have been used in experimental and clinical studies on MAS. This pilot study evaluated therapeutic potential of N-acetylcysteine in modulation of meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated adult rabbits were intratracheally given 4 ml/kg of meconium (25 mg/ml) or saline (Sal, n = 6). Thirty minutes later, meconium-instilled animals were treated with intravenous N-acetylcysteine (10 mg/kg, Mec + NAC, n=6) or were non-treated (Mec, n = 6). All animals were oxygen-ventilated for additional 5 hours. Total and differential blood leukocyte counts were determined at baseline, and at 1, 3 and 5 h of the treatment. After sacrificing animals, left lung was saline-lavaged and total and differential cell counts in the bronchoalveolar lavage fluid were determined. Right lung was used for biochemical analyses and for estimation of wet-dry weight ratio. In lung tissue homogenate, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation (LPO) products, and total antioxidant status (TAS) were detected. In isolated lung mitochondria, TBARS, dityrosine, lysine-LPO products, thiol group content, conjugated dienes, and activity of cytochrome c oxidase were estimated. To evaluate systemic effects of meconium instillation and NAC treatment, TBARS and TAS were determined also in plasma. To evaluate participation of eosinophils in the meconium-induced inflammation, eosinophil cationic protein (ECP) was detected in plasma and lung homogenate. Meconium instillation increased oxidation markers and ECP in the lung and decreased TAS (all P<0.05). NAC treatment reduced ECP and oxidation markers (all P<0.05, except of dityrosine in homogenate and conjugated dienes in mitochondria) and prevented a decrease in TAS (P<0.01) in lung homogenate compared to Mec group. In plasma, NAC decreased TBARS (P<0.001) and ECP, and increased TAS (both P<0.05) compared to Mec group. Concluding, N-acetylcysteine diminished meconium-induced inflammation and oxidative lung injury.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 02/2015; 66(1):101-10. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anti-inflammatory drugs are increasingly used for treatment of neonatal meconium aspiration syndrome (MAS), but their adverse effects are poorly known. Therefore, the aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine on cardiovascular parameters in an animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium suspension (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were given N-acetylcysteine (10 mg/kg, i.v.) or the same volume of saline. Changes in cardiovascular parameters (blood pressure, heart rate, and heart rate variability) were recorded over a 5-min course of solution administration, over 5 min after its end, and then hourly for 5 h. Oxidation markers (thiobarbituric acid-reactive substances (TBARS) and total antioxidant status) and aldosterone, as a non-specific marker of cardiovascular injury, were determined in plasma. Meconium instillation did not evoke any significant cardiovascular changes, but induced oxidative stress and elevated plasma aldosterone. N-acetylcysteine significantly reduced the mentioned markers of injury. However, its administration was associated with short-term increases in blood pressure and in several parameters of heart rate variability. Considering these effects of N-acetylcysteine, its intravenous administration in newborns with MAS should be carefully monitored.
Advances in Experimental Medicine and Biology 10/2014; 832. DOI:10.1007/5584_2014_4 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.
Advances in Experimental Medicine and Biology 10/2014; 832. DOI:10.1007/5584_2014_7 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperhomocysteinemia (hHCy) is recognized as a co-morbid risk factor of human stroke. It also aggravates the ischemia-induced injury by increased production of reactive oxygen species, and by the homocysteinylation and thiolation of functional proteins. Ischemic preconditioning represents adaptation of the CNS to sub-lethal ischemia, resulting in increased brain tolerance to subsequent ischemia. We present here an overview of recent data on the homocysteine (Hcy) metabolism and on the genetic and metabolic causes of hHCy-related neuropathologies in humans. In this context, the review documents for an increased oxidative stress and for the functional modifications of enzymes involved in the redox balance in experimentally induced hHCy. Hcy metabolism leads also to the redox imbalance and increased oxidative stress resulting in elevated lipoperoxidation and protein oxidation, the products known to be included in the neuronal degeneration. Additionally, we examine the effect of the experimental hHCy in combination with ischemic insult, and/or with the preischemic challenge on the extent of neuronal degeneration as well as the intracellular signaling and the regulation of DNA methylation. The review also highlights that identification of the effects of co-morbid factors in the mechanisms of ischemic tolerance mechanisms would lead to improved therapeutics, especially the brain tissue.
[Show abstract][Hide abstract] ABSTRACT: Elevated concentration of the homocysteine (Hcy) in human tissues, resulting either from mutations in genes enconding Hcy-metabolizing enzymes, or from deficiences of folic acid has recognized cytotoxic effect. Even a mild Hcy level increase is a risk factor for cardiovascular diseases and stroke in humans and also a risk factor for neurodegenerative disordes, such as dementia, or Alzheimer's disease. However, it is not yet clear whether homocysteine is a marker, or a causative agent. We present here an overview of recent data on the homocysteine metabolism and on the genetic and the metabolic causes of hyperhomocysteinemia-related pathologies in humans. In context of our results which detected an increased oxidative stress in hyperhomocysteinemic rats we discuss here the role of free radicals in this disorder. Imbalance between homocysteine auto-oxidation, production of reactive metabolites and cellular antioxidant defence induced by hyperhomocysteinemia results to cytotoxicity by oxidizing membrane lipids and proteins. Consequently, protein thiolation and homocysteinylation results in the structural and functional modifications of cells, including neuronal ones. It is our hope that identification of prophylacting factors effective in the prevention of toxic effect of Hcy would lead to improved therapeutics, especially the brain tissue.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 02/2014; 65(1):15-23. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various anti-inflammatory drugs have been used for treatment of neonatal meconium aspiration syndrome (MAS). As their adverse effects are poorly described, this study compared effects of selective phosphodiesterase (PDE) 3 inhibitor olprinone and non-selective PDE inhibitor aminophylline on cardiovascular parameters in animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were intravenously given olprinone (0.2 mg/kg) at a single dose at 0.5 h after meconium instillation, or aminophylline (2.0 mg/kg) at two doses at 0.5 and 2.5 h after meconium instillation, or were left without treatment. Cardiovascular changes were evaluated within 5 min of administration and 5 min after finishing the administration. Furthermore, respiratory and cardiovascular parameters were measured within 5 hours following treatment delivery. Oxidation markers (thiobarbituric acid-reactive substances (TBARS), and total antioxidant status) and markers of cardiovascular injury (aldosterone, gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)) were determined in the plasma. Meconium instillation induced acute lung injury associated with oxidative stress, elevated aldosterone, and slightly increased GGT and AST levels. Both aminophylline and olprinone improved lung functions and reduced oxidation stress. However, the PDE inhibitors acutely increased blood pressure and heart rate, whereas heart rate variability remained higher till the end of experiment and correlated well with markers of cardiovascular injury. Considering that systemic administration of olprinone and aminophylline was accompanied by acute cardiovascular changes in the meconium-instilled animals, use of PDE inhibitors in the newborns with MAS should be carefully monitored.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2013; 64(6):751-9. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).
[Show abstract][Hide abstract] ABSTRACT: Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.
Advances in Experimental Medicine and Biology 01/2013; 756:189-96. DOI:10.1007/978-94-007-4549-0_24 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
General Physiology and Biophysics 06/2012; 31(2):179-84. DOI:10.4149/gpb_2012_020 · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 04/2012; 63(2):179-86. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since inflammation and oxidation play a key role in the pathophysiology of neonatal meconium aspiration syndrome, various anti-inflammatory drugs have been tested in the treatment. This study evaluated whether the phosphodiesterase (PDE) 3 inhibitor olprinone can alleviate meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated rabbits intratracheally received 4 ml/kg of meconium (25 mg/ml) or saline. Thirty minutes after meconium/saline instillation, meconium-instilled animals were treated by intravenous olprinone (0.2 mg/kg) or were left without treatment. All animals were oxygen-ventilated for an additional 5 h. A bronchoalveolar lavage (BAL) of the left lungs was performed and differential leukocyte count in the sediment was estimated. The right lungs were used to determine lung edema by wet/dry weight ratio, as well as to detect oxidative damage to the lungs. In the lung tissue homogenate, total antioxidant status (TAS) was determined. In isolated lung mitochondria, the thiol group content, conjugated dienes, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation products, and activity of cytochrome c oxidase (COX) were estimated. To evaluate the effects of meconium instillation and olprinone treatment on the systemic level, TBARS and TAS were determined in the blood plasma, as well. Meconium instillation increased the relative numbers of neutrophils and eosinophils in the BAL fluid, increased edema formation and concentrations of oxidation markers, and decreased TAS. Treatment with olprinone reduced the numbers of polymorphonuclears in the BAL fluid, decreased the formation of most oxidation markers in the lungs, reduced lung edema and prevented a decrease in TAS in the lung homogenate compared to non-treated animals. In the blood plasma, olprinone decreased TBARS and increased TAS compared to the non-treated group. Conclusion, the selective PDE3 inhibitor olprinone has shown potent antioxidative and anti-inflammatory effects in the meconium-induced oxidative lung injury.
[Show abstract][Hide abstract] ABSTRACT: 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.
Neurochemical Research 04/2011; 36(8):1475-81. DOI:10.1007/s11064-011-0473-7 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxygen therapy is used for the treatment of various diseases, but prolonged exposure to high concentrations of O(2) is also associated with formation of free radicals and oxidative damage.
In the present study we compared alpha-ketoglutarate dehydrogenase (KGDH) activity and mitochondrial oxidative damage in the hearts of guinea pigs after long-term (17 and 60 h) oxygenation with 100% normobaric O(2) and with partially negatively (O(2 neg)) or positively (O(2 posit)) ionized oxygen.
Inhalation of O(2) led to significant loss in KGDH activity and thiol group content and accumulation of bityrosines. Inhalation of O(2 neg) was accompanied by more pronounced KGDH inhibition, possibly due to additional formation of protein-lipid conjugates. In contrast, O(2 posit) prevented loss in KGDH activity and diminished mitochondrial oxidative damage.
These findings suggest that oxygen treatment is associated with impairment of heart energy metabolism and support the view that inhalation of O(2 posit) optimizes the beneficial effects of oxygen therapy.
European journal of medical research 12/2009; 14 Suppl 4(Suppl 4):116-20. DOI:10.1186/2047-783X-14-S4-116 · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Combination of low-dose budesonide and low-dose aminophylline may improve lung function in reduced adverse effects compared with high-dose monotherapy. Adult rabbits intratracheally received 4 ml/kg of saline or meconium (25 mg/ml). Meconium-injured rabbits were treated at 0.5 and 2.5 h after meconium instillation by intravenous aminophylline (1.0 mg/kg), by intratracheal budesonide (0.125 mg/kg) followed by intravenous aminophylline (1.0 mg/kg), or were untreated. Although aminophylline improved some respiratory parameters, budesonide+aminophylline more effectively reduced intrapulmonary shunts and improved gas exchange, without significant cardiovascular effects. Combined treatment reduced lung edema and number of lung neutrophils to a higher extent than aminophylline alone. Both treatments reduced lung peroxidation and in vitro airway reactivity to histamine, with a better effect after aminophylline alone. Combination of budesonide and aminophylline enhanced respiratory parameters more effectively, having fewer side effects than aminophylline alone. However, no additive effect of budesonide was observed on lung peroxidation and in vitro airway reactivity.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:461-71. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medical oxygen. Guinea pigs inhaled air, 100% molecular medical oxygen (O(2)mol), partially negatively (O(2)neg) or positively (O(2)posit) ionized oxygen during 17 and 60 h. After 17 h, dityrosines, markers of oxidative injury, in lung homogenate increased in O(2)neg and decreased in O(2)posit groups vs. controls. After 60 h, dityrosines rose after inhalation of O(2)mol and O(2)neg, but not in the O(2)posit group. Lysine-LPO products increased and lung wet/dry weight ratio decreased in O(2)mol and O(2)neg, and not in O(2)posit group. Relative neutrophil count in BALF was elevated in all oxygen-treated groups with lower numbers in O(2)posit vs.O(2)mol and O(2)neg groups. After 60 h, surfactant activity was better in O(2)posit vs. O(2)mol group. In conclusion, long-term inhalation of partially positively ionized oxygen is associated with less oxidative stress, milder lung inflammatory response, and better surfactant activity than molecular or negatively ionized oxygen.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:173-81. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Due to missing information on appropriate dosing of aminophylline in meconium aspiration syndrome (MAS), this study compared effects of high-dose and low-dose aminophylline on lung function of animals with MAS. Meconium-instilled rabbits were treated by low-dose (LD, 1.0 mg/kg), or high-dose (HD, 2.0 mg/kg) aminophylline at 0.5 and 2.5 h after meconium instillation, or were left untreated. Within 5 h of oxygen ventilation, HD-aminophylline improved gas exchange, reduced pulmonary shunts and ventilatory pressures, and decreased edema formation and lung neutrophils. LD-aminophylline enhanced lung function to a lower extent than HD-aminophylline, and failed to reduce lung edema and the number of lung neutrophils. Both treatments decreased lung peroxidation, with a stronger effect of HD-aminophylline on lipid oxidation and of LD-aminophylline on protein oxidation. Tracheal reactivity to histamine decreased after HD-aminophylline, while lung tissue reactivity was more reduced after LD-aminophylline. Although LD-aminophylline showed some anti-inflammatory potential, HD-aminophylline improved most of the parameters more effectively.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:449-59. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoids may improve lung function in newborns with meconium aspiration syndrome (MAS), but information on the acute side effects of glucocorticoids in infants is limited. In this study using a rabbit model of MAS, we addressed the hypothesis that systemic administration of dexamethasone causes acute cardiovascular changes. Adult rabbits were treated with 2 intravenous doses of dexamethasone (0.5 mg/kg each) or saline at 0.5 h and 2.5 h after intratracheal instillation of human meconium or saline. Animals were oxygen-ventilated for 5 h after the first dose of treatment. Blood pressure, heart rate, and short-term heart rate variability (HRV) were analyzed during treatment, for 5 min immediately after each dose, and for the 5 h of the experiment. In the meconium-instilled animals, dexamethasone increased blood pressure, decreased heart rate, increased HRV parameters, and caused cardiac arrhythmia during and immediately after administration. In the saline-instilled animals, the effect of dexamethasone was inconsistent. In these animals, the acute effects of dexamethasone on blood pressure and cardiac rhythm were reversed after 30 min, whereas heart rate continued to decrease and HRV parameters continued to increase for 5 h after the first dose of dexamethasone. These effects were more pronounced in meconium-instilled animals. If systemic glucocorticoids are used in the treatment of MAS, cardiovascular side effects of glucocorticoids should be considered.
Canadian Journal of Physiology and Pharmacology 12/2008; 86(11):804-14. DOI:10.1139/Y08-086 · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surfactant lung lavage is a promising approach in the treatment of meconium aspiration syndrome (MAS). We hypothesise that the enrichment of modified natural surfactant with dextran will enhance meconium clearance from the airspaces during lung lavage and improve lung function in experimental MAS. Human meconium (30 mg/ml; 4 ml/kg) was instilled into the tracheal cannula of anaesthetised and paralysed adult rabbits to induce respiratory failure. The animals were then lavaged with saline (Sal), surfactant without (Surf) and with dextran (Surf+dex). Lung lavage (10 ml/kg in three portions) was performed with diluted surfactant (Curosurf, 10 mg/ml, 100 mg/kg) without or with dextran (3 mg/mg of surfactant phospholipids) or saline and the animals were conventionally ventilated with 100% O(2) for an additional hour. Lung functions were measured prior to and after meconium instillation, and 10, 30 and 60 min after lavage. The recovery of meconium in bronchoalveolar lavage (BAL) fluid was quantified. More meconium solids was recovered in the surfactant-lavaged than in the saline-lavaged groups (Surf: 12.4 +/- 3.9% and Surf+dex: 17.5 +/- 3.5% vs. Sal: 4.8 +/- 1.0%; both P < 0.01). Moreover, more meconium solids was obtained by Curosurf/dextran than by Curosurf-only lavage (P < 0.05). In the Surf group, the values for PaO(2)/FiO(2) were significantly higher than in the controls (at 60 min: 24.5 +/- 4.2 kPa vs.9.1 +/- 2.2 kPa, P < 0.01). An additional increase in oxygenation was seen in the Surf+dex group (at 60 min: 34.2 +/- 8.1 kPa, P vs. Surf group <0.01). The lung-thorax compliance was higher in the Surf+dex group in comparison with the Sal and Surf groups (at 60 min: 9.6 +/- 0.9 vs.7.6 +/- 1.2, P < 0.01 and 8.0 +/- 0.7 ml/kPa/kg, P < 0.05). The enrichment of Curosurf with dextran improves meconium clearance and lung functions in surfactant-lavaged rabbits with meconium aspiration.
European Journal of Pediatrics 08/2008; 167(8):851-7. DOI:10.1007/s00431-007-0596-7 · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Free radicals play an important role in the pathogenesis of brain injury. This study evaluates the potential relationship between ischaemia/reperfusion (I/R)-induced brain injury, peripheral oxidative stress (lymphocyte DNA damage), plasma antioxidant potential and uric acid levels. We observed that 15 min of ischaemia were sufficient to significantly increase lymphocyte DNA damage that remained elevated at the end of early (3 h) reperfusion and at later (72 h) reperfusion time; this parameter was not significantly increased, when compared to preoperated levels. In parallel, antioxidant potential was elevated after 15 min of ischaemia, remained high at early (3 h) reperfusion and decreased again with longer (72 h) reperfusion. A close association between the plasma antioxidant status and the uric acid content has been confirmed by findings that changes in TRAP values positively correlate with uric acid concentration in rat plasma after ischaemic injury. Moreover, results of in vitro experiments with extra uric acid addition to control plasma have shown that uric acid contributes to a greater part of TRAP values. These results indicate a similar time course of brain I/R-associated oxidative stress and peripheral antioxidant defence status and/or oxidative stress in animal experiments.