A randomized controlled trial comparing isosorbide dinitrate-oxytocin versus misoprostol-oxytocin at management of foetal intrauterine death.

BACKGROUND: The metabolic activity of endogenous nitric oxide (NO) and the medical use of nitrovasodilatory drugs like isosorbide dinitrate have been shown to be potential inducers inducers of cervical ripening prior to surgical evacuation of the uterus. OBJECTIVE: To assess the therapeutic efficacy and safety of combined isosorbide dinitrate-oxytocin in the management of intrauterine foetal death (IUFD). METHODS: Sixty women with IUFD after 20 weeks of gestation requesting uterine evacuation were randomly selected to receive isosorbide dinitrate gel solution (80 mg/1.5 mL; n = 30) or misoprostol gel solution (100 mcg/1.5 mL; n = 30) every 3 h with a maximum of four doses or until a Bishop score >7 was reached. Subsequently, patients received a high dose of intravenous oxytocin until complete uterus evacuation was achieved. Therapeutic efficacy was evaluated by mean the relative risk of the foetal expulsion based on comparison of event rates, and the proportion of women induced to labor at 7, 10 and 15 h after the administration of isosorbide dinitrate or misoprostol. Safety was assessed on the basis of woman´s vital signs and evaluation of adverse effects, including headache, abdominal pain, pelvic pain, lower back pain, nausea, dizziness and vomiting. RESULTS: The foetal expulsion rate using the isosorbide dinitrate-oxytocin combination was approximately 4.4 times, and at least 2.1 times, the foetal expulsion rate with the misoprostol-oxytocin regimen at any given point in time. The proportion of women achieved vaginal delivery at 15 hours was 100% for the isosorbide dinitrate-oxytocin group and 86.7% for the misoprostol-oxytocin group. The average delivery induction interval was significantly lower when isosorbide dinitrate-oxytocin was used (8.7 ± 3.1 h) than when misoprostol-oxytocin (11.9 ± 3.1 h) was used. A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. CONCLUSION: This study indicates that intravaginal isosorbide dinitrate followed by intravenous oxytocin was more effective than the conventional method used to induce labour in the medical management of foetal death in pregnancies after 20 weeks of gestation. TRIAL REGISTRATION: Clinicaltrials.gov NCT02488642.

Lysosomal dysfunction induced by changes in albumin's tertiary structure: Potential key factor in protein toxicity during diabetic nephropathy.

AIMS: Increased amounts of protein, in particular albumin within renal tubular cells (TBCs), induce the expression of inflammatory and fibrogenic mediators, which are adverse prognostic factors in tubulointerstitial fibrosis and diabetic nephropathy (DN). We sought to assess the participation of the thiol-linked tertiary structure of albumin in the mechanism of protein toxicity in a model of TBCs. MATERIALS AND METHODS: Cultured human renal proximal tubular cells, HK-2, were exposed to isolated albumin from patients with and without DN (Stages 0, 1 and 4). The magnitude of change of the albumin tertiary structure, cell viability (LDH leakage), apoptosis (Annexin V), transdifferentiation and reticulum endoplasmic stress (Western blot and flow cytometry) and lysosomal enzyme activity were assessed. KEY FINDINGS: We found that albumin from Stage 4 patients presented >50% higher thiol-dependent changes of tertiary structure compared to Stages 0 and 1. Cells incubated with Stage 4 albumin displayed 5 times less viability, accompanied by an increased number of apoptotic cells; evidence of profibrogenic markers E-cadherin and vimentin and higher expression of epithelial-to-mesenchymal transition markers α-SMA and E-cadherin and of endoplasmic reticulum stress protein GRP78 were likewise observed. Moreover, we found that cathepsin B activity in isolated lysosomes showed a significant inhibitory effect on albumin from patients in advanced stages of DN and on albumin that was intentionally modified. SIGNIFICANCE: Overall, this study showed that thiol-dependent changes in albumin's tertiary structure interfere with the lysosomal proteolysis of renal TBCs, inducing molecular changes associated with interstitial fibrosis and DN progression.

Increased systemic and peritoneal oxidative stress biomarkers in endometriosis are not related to retrograde menstruation.

Objetives: The goal of this study was to determine if systemic and peritoneal oxidative stress biomarkers are related to each other and to retrograde menstruation in endometriosis. Methods: Plasma and peritoneal fluid oxidative stress biomarkers and hemoglobin and erythrocytes in peritoneal fluid as retrograde menstruation indicators, were measured in 28 patients with endometriosis and 23 without endometriosis. Results: In the peritoneal fluid, carbonyls and lipohydroperoxides, indicative of protein and lipid oxidative damage, were higher in endometriosis group (21%, p = 0.016 and 46%, p = 0.009, respectively). However, these biomarkers were not different in the blood plasma of both groups, and only protein dityrosine, was increased in the plasma of endometriosis group (31%, p = 0.04). The peritoneal fluid hemoglobin content was not higher in the endometriosis group, nor related to carbonyls and lipohydroperoxides. Additionally, the peritoneal fluid oxidative biomarkers were not correlated with the blood plasma ones, and only malondialdehyde, and ischemia-modified albumin were almost two times higher in peritoneal fluid. Discussion: Our results show a peritoneal and systemic oxidative stress biomarkers increase in endometriosis, but not related to each other, and do not support the hypothesis of an increase in hemoglobin-iron supply towards the peritoneal cavity that causes oxidative damage.

Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells?

Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14.

Oxidative stress biomarkers and their relationship with cytokine concentrations in overweight/obese pregnant women and their neonates.

BACKGROUND: Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. RESULTS: Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1ß. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1ß in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. CONCLUSIONS: Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth.

Urban PM2.5 activates GAPDH and induces RBC damage in COPD patients.

During Chronic Obstructive Pulmonary Disease (COPD) progression, the intracellular antioxidant defence in RBCs must preserve the integrity of the plasmalemma through NADPH+ generation to obtain a sufficient number of reduced non-protein SH-groups. Here, we studied the activities of enzymes in RBCs that are related to glutathione metabolism under conditions of increasing oxidative stress, which are associated with COPD progression, by increasing cellular damage in vitro with PM2.5, a ROS generator. The study included 43 patients, who were separated according to their GOLD classification into moderate and severe groups, along with 11 healthy volunteers (HV). Blood samples were analysed for G6PD, GAPDH, GPx, and GR. The results showed significant decreases in the oxidation of the G6PD, GR and GPx proteins, resulting in decreased enzymatic activity. By contrast, an increase (p<0.05) in GAPDH was observed, suggesting a pool of ATP on the membrane. However, it is evident that RBCs are damaged during the progression of COPD, although their integrity is preserved, and they retain limited function, thus allowing patient survival without haemolysis.

Urban PM2.5 induces ROS generation and RBC damage in COPD patients.

Particulate matters (PM) produce adverse effects on the respiratory system and cause COPD. These effects are thought to involve intrinsic generation of ROS which are present in ambient PM (transition metals and aromatic organic compounds). Here, we examined the chemical composition and ultra-microscopic structure of PM2.5. The effect of this PM was studied in red blood cell (RBC) membranes (ghosts) from healthy volunteers (n = 11) and COPD patients (n = 43). These effects were compared with that produced by a Fenton metal-catalytic ROS generator. Oxidative biomarkers and cell damage were singificantly increased in presence of PM2.5 or ROS generator in RBC of COPD patients as compared with those in cells from healthy volunteers. In contrast, total SH groups, band 3 phospho-tyrosine phosphatase (PTPase) and glucose-6 phosphate dehydrogenase (G6PD) activities were all diminished in cells from COPD patients. In conclusion, PM2.5 increases damage to RBCs from COPD patients, decreases the activity of PTPase and G6PD, and alters the function of the anionic exchanger (AE1) and the antioxidant response by decreasing SH groups.

Increased platelet and erythrocyte arginase activity in chronic obstructive pulmonary disease associated with tobacco or wood smoke exposure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that is characterized by a progressive and irreversible decline in lung function and is caused primarily by chronic exposure to tobacco and to wood smoke. It is linked to oxidative stress and to an up-regulation of airway arginases and is also associated with alterations in platelets and erythrocytes. In the present study, arginase activity was studied in platelets and erythrocytes of 2 groups of COPD patients: 31 tobacco ex-smokers and 27 patients who had been exposed to wood smoke. A total of 15 healthy controls were also included. METHODS: Plasma, platelets, and erythrocytes were obtained from the blood samples. Levels of the oxidative stress biomarkers, carbonyls and malondialdehyde, were measured in the plasma, and arginase activity was quantified in platelets and erythrocytes. RESULTS: In both groups of COPD patients, an increase in the oxidative stress biomarkers was found. Platelet arginase activity in both COPD groups was 2-fold higher than that in the control group. In the erythrocytes, the arginase activity increased 1.7-fold over the control only in the wood smoke-induced COPD group. DISCUSSION AND CONCLUSIONS: These results suggest that the increase in arginase activity in platelets and erythrocytes participates in the alteration in nitric oxide metabolism in COPD patients and that there may be some differences between the tobacco smoke- and wood smoke-induced COPD.

RBC membrane damage and decreased band 3 phospho-tyrosine phosphatase activity are markers of COPD progression.

Injury to red blood cell (RBC) membrane by oxidative stress is of clinical importance in chronic obstructive pulmonary disease (COPD) which leads to oxidative stress (OE) during disease progression. Here, we studied the impact of this stress on injury to RBC membrane. Blood samples from both healthy volunteers (HV, n = 11) and controlled COPD patients (n=43) were divided according to their GOLD disease stage (I=7, II=21, III=10, IV=5). Plasma levels of paraoxonase (PON) activity, protein carbonyls (PC), conjugate dienes, lipohydroperoxides (LPH) and malondialdehyde (MDA) were determined and the PTPase, and the oxidative parameters were measured in RBC ghosts. Plasma from patients with COPD showed an increased oxidation of lipids and proteins, that correlated with the disease progression. PON activity decreased from GOLD stages II to IV and correlated with an increase in LPH (p less than 0.0001, r = -0.8115). There was evidence of an increase in the oxidative biomarkers in RBCs, while the PTPase activity was diminished in stage III and IV of COPD. In conclusion, OE-induced injury associated with COPD is associated with an oxidative damage to the RBC membrane, with a concomitant decrease in the PTPase activity and altered function of anionic exchanger (AE1).

Structural and functional changes in the insulin molecule produced by oxidative stress.

The change produced by oxidative stress on proteins (cross-links, backbone cleavage, amino acid modification) generates structural changes with a wide range of consequences such as increased propensity to the aggregation or proteolysis, altered immunogenicity and frequently enzymatic and binding inhibition. Insulin is particularly sensitive to conformational changes, aggregation and cross-linking; any change on insulin could impair its function. We have examined the biological activity of insulin modified by hydroxyl radical and exposed to acrolein in rats and adiposites. We found out important changes that we have shown as prototype of possible effect of oxidative stress on the structural and functional damage to insulin. Whereas, hydroxyl radical and acrolein both have diminished the hypoglycemic effect of insulin in vivo, and the effect of acrolein seems be to involved in carbonylation and not derived from inter-molecular cross-links formation or aggregates. The effect was highly stimulated at alkaline pH, concomitant with carbonyl formation and then probably aldolic condensation type reaction-dependent. Hydroxyls radical generates tyrosine derivative formation and introduces non aldehyde dependent carbonyls in the insulin molecule.

Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach.

BACKGROUND: The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. METHODS: In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. RESULTS: Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). CONCLUSION: These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group.On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.

Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes.

Lipid peroxidation induced by reactive oxygen species might modify circulating biomolecules because of the formation of alpha,beta-unsaturated or dicarbonylic aldehydes. In order to investigate the interaction between a lipoperoxidation product, acrolein, and a circulating protein, insulin, the acrolein-insulin adduct was obtained. To characterize the adduct, gel filtration chromatography, sodium dodecylsulfate-polyacrylamide gel electrophoresis and carbonyl determination were performed. Induction of hypoglycemia in the rat and stimulation of glucose uptake by 3T3 adipocytes were used to evaluate the biological efficiency of the adduct compared with that of native insulin (Mackness, B., Quarck, R., Verte, W., Mackness, M., and Holvoet, P. (2006) Arterioscler., Thromb. Vasc. Biol. 26, 1545-1550). Formation of the acrolein-insulin complex in vitro increased the carbonyl group concentration from 2.5 to 22.5 nmol/mg of protein, and it formed without intermolecular aggregates (Halliwell, B., and Whiteman, M. (2004) Br. J. Pharmacol. 142, 231-255. The hypoglycaemic effect 18 min after administration to the rat is decreased by 25% (Robertson, R. P. (2004) J. Biol. Chem. 279, 42351-42354. An adduct concentration of 94 nM, compared to 10 nM for native insulin, was required to obtain the A 50% (concentration needed to obtain 50% of maximum transport of glucose uptake by 3T3 adipocytes). In conclusion, formation of the acrolein-insulin adduct modifies the structure of insulin and decreases its hypoglycemic effect in rat and glucose uptake by 3T3 adipocytes. These results help explain how a toxic aldehyde prone to be produced in vivo can structurally modify insulin and change its biological action.

La función plaquetaria más allá de la hemostasis: participación en las enfermedades respiratorias / Platelet function beyond haemostasis: Role in respiratory diseases

Actualmente se sabe que las plaquetas, además de almacenar diversos mediadores químicos, también tienen la capacidad de realizar síntesis de varios tipos de proteínas a partir de ARN preformados y de interaccionar con diversos tipos de partículas, con componentes de la matriz extracelular y con varios tipos celulares. Estas características posibilitan que las plaquetas intervengan activamente, no sólo en la hemostasis y trombosis, sino también en la inflamación, remodelación tisular y posiblemente en la defensa innata.

Platelets store different chemical mediators and synthetize various types of proteins from preformed RNA; they also interact with different particles, components of the extracellular matrix and with different kinds of cells. This characteristics enable platelets to have important roles In hemostasis, thrombosis, inflammation, tissue remodeling and possibly in mechanisms of innate defense.

Oxidation by reactive oxygen species (ROS) alters the structure of human insulin and decreases the insulin-dependent D-glucose-C14 utilization by human adipose tissue.

The formation of dityrosine of human insulin oxidized by metal-catalyzed oxidation system (H2O2/Cu) was estimated by fluorescent methods. The oxidation of tyrosine and phenylalanine residues present on the insulin molecule was evident after 2 minutes of in vitro oxidation due to the formation of protein-bound dityrosine. The success of oxidative protein modification was followed until available aromatic residues were consumed (60 minutes), measured by their emission at 405 nm. The structural and chemical changes on insulin molecule are related to the loss of biological activity as assessed by measuring the increase of U-14C-glucose utilization by human adipose tissue in a radiorespirometry system. The oxidation of glucose (14CO2 production) of the adipose cells was increased 35 % (301 +/- 119 to 407 +/- 182 cpm/mg in dry weight. P < 0.05) in presence of 0.1 IU and 69 % (301 +/- 119 to 510 +/- 266 cpm/dry weight. P < 0.05) for 1.0 IU of insulin. The recombinant human insulin oxidized for 5 minutes only increased the glucose oxidation by 25 %. In conclusion, these observations show that dityrosine formation and other oxidative chemical changes of insulin due to its in vitro oxidation decrease and can abolish its biological activity.

Perspectivas del uso de antioxidantes como coadyuvantes en el tratamiento del asma / Perspectives in the use of antioxidants for the treatment of asthma

Al tratarse de un proceso inflamatorio, en el asma hay participación e incremento en la generación de especies reactivas del oxígeno, dando lugar a un desequilibrio oxidante/antioxidante, fenómeno que se ha descrito como estrés oxidante, que causa daño a diferentes biomoléculas. La utilización de agentes antioxidantes exógenos o activadores de antioxidantes endógenos como coadyuvantes de la terapéutica del paciente asmático, es una posibilidad a discutir.

Oxidative stress seen in bronchial asthma can damage different kinds of biomolecules; this oxidant/antioxidant imbalance results from an increment in the production of oxygen reactive species. The utilization of exogenous antioxidant agents or promoters of endogenous antioxidants can be seen as an alternative therapy for asthma that is worth discussing.

Estrés oxidante en asma / Oxidative stress in asthma

El asma es una enfermedad inflamatoria crónica del tracto respiratorio de etiología aún desconocida; sin embargo, nuevas evidencias han involucrado al estrés oxidante, en el que la participación e incremento en la generación de especies reactivas del oxígeno por diferentes sistemas bioquímicos, superan a los mecanismos antioxidantes en el ambiente de las vías respiratorias del asmático, lo cual es acompañado de alteraciones inducidas por radicales libres que involucran daño estructural y modificaciones metabólicas presentes, a nivel sistémico y en el tracto respiratorio.

Asthma is a chronic inflammatory disease of the airways: its precise etiology is still unknown. New evidence points to oxydative stress, in which the participation and increment of reactive species of oxygen by several biochemical systems overwhelms the anti oxidant mechanisms of the airways; this, in conjunction with changes induced by free radicals involving systemic and local respiratory structural damage and metabolic changes.

Peroxynitrite activates glucose uptake in 3T3-L1 adipocytes through a PI3-K-dependent mechanism.

Peroxynitrite, the product of the reaction between *NO and O2*-, is a strong oxidant and nitrating molecule, and it has been recently consideredas a component of some important signaling pathways. Herein, we report the effect of peroxynitrite on glucose uptake in 3T3-L1 adipocytes. Peroxynitrite stimulated glucose uptake and this effect was inhibited by citochalasin B, indicating the participation of facilitated GLUT transporters. Peroxynitrite-induced glucose uptake was not related to intracellular ATP, nor to external or internal calcium, but it was inhibited by the phosphatidylinositol 3-kinase (PI3-K) inhibitor, wortmannin. Additionally, we also found that peroxynitrite did not activate the insulin receptor nor the PI3-K downstream signaling protein kinase B (PKB/Akt). The dose-dependent inhibitory action of wortmannin suggests that peroxynitrite activates glucose transport without affecting GLUT transporters translocation.

Reactive oxygen species (ROS) induce chemical and structural changes on human insulin in vitro, including alterations in its immunoreactivity.

Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the endogenous antioxidant defense. Peroxidations induced by ROS are the key of chemical and structural modifications of biomolecules including circulating proteins. To elucidate the effect of ROS on circulating proteins and considering the presence of oxidative stress in Diabetes Mellitus, the effects of ROS, in vitro, on human insulin were studied. We utilized the Fenton reaction for free hydroxyl radical (HO*) generation in presence of human recombinant insulin measuring chemical changes on its molecular structure. The induced changes in insulin were: a) significant increase on absorbance (280 nm) due to phenylalanine hydroxylation (0.023 +/- 0.007 to 0.13 +/- 0.07). b) Peroxidation products formed on amino acids side branches (peroxyl and alcohoxyl group); measured as increased capacity of reduce nitroblue of tetrazolium (NBT) to formazan (0.007 +/- 0.007 to 0.06 +/- 0.02). c) Increased concentration of free carbonyl groups (8.8 +/- 8.7 to 45.6 +/- 20.2 pmoles dinitrophenylhidrazones/nmol insulin) with lost of secondary structure, and d) Modification of epithopes decreasing the insulin antigen-antibody reactivity measured as a decrease in insulin concentration by RIA. In conclusion, the radical hydroxyl in vitro is able to induce molecular modifications on insulin.

Participación d las especies reactivas del oxígeno en las enfermedades pulmonares

Las especies reactivas de oxígeno son moléculas (O2•-, HO • , NO • ), muy reactivas debido a que en el último orbital tienen un electrón no pareado (radical libre), lo cual confiere inestabilidad física. Se incluyen en las especies reactivas de oxígeno a moléculas precursoras de los radicales libres (H2O2, HONO2-). Estas especies participan en procesos fisiológicos en el organismo. Cuando la generación de especies reactivas de oxígeno supera a los mecanismos de inactivación, se presenta el estado metabólico de estrés oxidante que se caracteriza por daños moleculares y celulares que conducen a predisposición o modificación de diversos padecimientos crónico-degenerativos. Entre las enfermedades pulmonares en que se ha demostrado la participación de las especies reactivas de oxígeno, destacan el síndrome de insuficiencia respiratoria progresiva, la enfermedad pulmonar obstructiva crónica y el asma. Se analizan las características del estrés oxidante en estos padecimientos.

Reactive Oxygen Species (ROS) are very reactive molecules (O2•-, HO•, NO• ) since they have a single and unpaired electron in the last orbital (free radical) which confers them physical instability. Free radical precursors such as H2O2 , HONO2- are considered ROS. These species are important in the physiological processes. When ROS production exceeds the inactivation mechanisms, oxidative stress takes place. This stress is characterized by molecular and cellular damage which predisposes to or modifies chronic-degenerative diseases. Among pulmonary diseases in which ROS participation has been proved are ARDS, COPD and asthma. The aim of this paper was to analyze the mechanisms of oxidative stress that lead to those illnesses.