Methemoglobin Concentration Research Articles

Protective effect of placenta extracts against nitrite-induced oxidative stress in human erythrocytes.

Aqueous-saline human placenta extract (HPE) is known to possess antioxidant activity due to the high concentration of bioactive substances. This fact allows its application in clinical practice in order to treat oxidation-induced diseases. Extract antioxidant activity is mainly conditioned by proteins. Freezing of extracts has been shown to lead to their antioxidant activity increasing due to protein conformation changes.Different biological models are widely used in order to evaluate efficacy of novel antioxidants and mechanisms of their action. One such model appears to be erythrocytes under nitrite-induced oxidative stress. Nitrite is known to be able to penetrate erythrocyte membrane and to oxidize hemoglobin. In order to investigate whether HPE is able to decrease nitrite-induced oxidative injuries and to evaluate the protein contribution to this process, spectrophotometric and electron spin resonance (ESR) assays were used.Experimental data have revealed that antioxidant activity of extracts and of some of their fractions correlates with methemoglobin concentration lowering. Preliminary erythrocyte incubation with an extract fraction of 12 kDa allows preservation of the structural-dynamic cytosol state the closest to the control.

Methemoglobinemia in children

All pigments of hemoglobin (oxyhemoglobin, methemoglobin, sulphemoglobin and carboxyhemoglobin) are of clinical importance and each has a laboratorial characteristic in the absorption spectrum. Methemoglobin, in which the ferrous iron atom of the heme group has been oxidized to a ferric iron atom, is unable to carry molecular oxygen. Various red cell enzymes convert methemoglobin back to oxyhemoglobin and keep the level of this pigment between 1% and 3%. High levels of methemoglobin (= 5%) are associated with chocolate-colored blood, cyanosis, headaches, tachycardia, dyspnea and tachypnea and in severe methemoglobinemia coma and death can occur.(1) Newborns are more susceptible to methemoglobinemia because fetal hemoglobin (Hb F) is easily oxidized.(2) Methemoglobin may arise from three different causes: 1. An excessive formation of methemoglobin due to contamination by chemical products, such as phenacetin, nitro or amino derivatives of benzene, derivatives of sulfur, etc. These products cause toxic methemoglobinemia.(3) 2. Inherited enzyme deficiencies including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and NADH-linked methemoglobin reductase or diaphorase. These enzyme deficiencies are inherited as Mendelian recessive conditions and are responsible for dramatic cases of cyanosis and hemolytic anemias.(4) 3. Methemoglobinemia due to abnormalities of the beta and alpha globins, especially those near to the heme group region. This abnormal form of oxidized hemoglobin is referred as hemoglobin M (Hb M) and there are at least six different types: Hb M Boston, a variant hemoglobin caused by a mutation in alpha globin (alpha 58 His → Tyr), Hb M Iwate (alpha 87 His → Tyr), Hb M Saskatoon (Beta 63 His → Tyr), Hb M Zurich (Beta 63 His → Arg), Hb M Hyde Park (Beta 92 His → Tyr) and Hb M Milwaukee (Beta 67 Val → Glu).(1,5) The article Reference values for methemoglobin concentrations in children(6) published in this issue of the Revista Brasileira de Hematologia e Hemoterapia showed that the methemoglobin levels in 6- to 10-year-old children are higher than those of healthy adults. The authors suppose that the difference in levels is due by a smaller amount of soluble cofactor cytochrome b5 and less activity of cytochrome b5 reductase in the red blood cells of children. However these enzymatic activities were not evaluated by the authors. So, should not factors (school, food, water, etc) in the environmental where the children of this investigation live be considered as a possible cause of the increased levels of methemoglobin?(3,4,7)

Nitrite Attenuates Ischemia-Reperfusion–Induced Microcirculatory Alterations and Mitochondrial Dysfunction in the Microvasculature of Skeletal Muscle

Recently, nitrite has been rediscovered as a physiologically relevant storage reservoir of nitric oxide in blood and it can readily be converted to nitric oxide under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of nitrite on reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle. The authors used a vascular pedicle isolated rat cremaster model that underwent 4 hours of warm ischemia followed by 2 hours or 17 hours of reperfusion. At 5 minutes before reperfusion, normal saline, sodium nitrite (0.20 μM/minute/kg), or nitrite mixed with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (potassium salt) (0.2 mg/minute/kg) was infused into the microcirculation of ischemic cremaster by means of intraarterial infusion. Ischemia-reperfusion-induced microcirculatory alterations were measured after 2 hours of reperfusion. Microvasculature of the cremaster muscle including the vascular pedicle was harvested to determine the mitochondrial dysfunction. The blood concentration of methemoglobin was also measured to determine the toxicity of nitrite. The authors found that nitrite significantly attenuated ischemia-reperfusion-induced vasoconstriction, arteriole stagnation, and capillary no-reflow in the early phase of reperfusion and the depolarization of mitochondrial membrane potential and cytochrome c release in the late phase of reperfusion. Nitrite-induced protection was significantly blocked by a nitric oxide scavenger (potassium salt). The methemoglobin results showed that the doses of nitrite we used in the present study were safe. The supplementation of a low dose of nitrite, directly into the microcirculation of ischemic muscle through local intraarterial infusion, significantly attenuated ischemia-reperfusion-induced microcirculatory alterations in vivo and mitochondrial dysfunction in vitro in the microvasculature of skeletal muscle.

The Current Status of Continuous Noninvasive Measurement of Total, Carboxy, and Methemoglobin Concentration

Intraoperative early detection of anemia, identifying toxic levels of carboxyhemoglobin after carbon monoxide exposure and titrating drug dosage to prevent toxic levels of methemoglobin are important goals. The pulse oximeter works by illuminating light into the tissue and sensing the amount of light absorbed. The same methodology is used by laboratory hemoglobinometers to measure hemoglobin concentration. Because both devices work in the same way, efforts were made to modify the pulse oximeter to also measure hemoglobin concentration. Currently there are 2 commercial pulse oximeters (Masimo Rainbow SET and OrSense NBM-200MP) that measure total hemoglobin concentration and one (Masimo) that also measures methemoglobin and carboxyhemoglobin. In this review, we describe the peer-reviewed literature addressing the accuracy of these monitors.

‘Safe’ Methaemoglobin Concentrations are a Mortality Risk Factor in Patients Receiving Inhaled Nitric Oxide

Inhaled nitric oxide (iNO) can reduce pulmonary arterial hypertension and improve oxygenation in some patients with severe respiratory or heart failure. Despite this, iNO has not been found to improve survival. This study aimed to perform a local practice audit to assess the mortality predictors of critically ill patients who had received iNO as therapy for pulmonary hypertension and respiratory or heart failure. A retrospective audit in a single tertiary centre intensive care unit of patients receiving iNO was conducted between 2004 and 2009. The indications for iNO use, comorbidities, severity of illness, organ function, oxygenation, Sequential Organ Failure Assessment scores, patterns of iNO use, adverse events and outcomes were reviewed. In 215 patients receiving iNO, improvement in oxygenation after one hour from iNO commencement did not predict either intensive care unit (P = 0.36) or hospital (P = 0.72) mortality. The independent risk factors for intensive care unit mortality were worsening Sequential Organ Failure Assessment scores within 24 hours of commencing iNO (adjusted odds ratio 1.07, 95% confidence interval 1.05 to 1.18), the Charlson Comorbidity Score (adjusted odds ratio 1.49, 95% confidence interval 1.16 to 1.91) and the peak methaemoglobin concentration in arterial blood while receiving iNO (adjusted odds ratio 2.67, 95% confidence interval 1.42 to 4.96). Inhaled nitric oxide as salvage therapy for severe respiratory failure in critically ill patients is not routinely justified. Increased methaemoglobin concentration during iNO therapy, even when predominantly less than 3%, is associated with increased mortality.

The Tumor Lysis Syndrome

TO THE EDITOR: We recently admitted a patient to our intensive care unit with methemoglobinemia and severe hemolytic anemia after he received a single dose of rasburicase. The patient was 55-year-old black man with chronic lymphocytic leukemia in whom the tumor lysis syndrome developed after rituximab and bendamustine treatment despite saline and allopurinol prophylaxis. Within 6 hours after receiving rasburicase at dose of 0.2 mg per kilogram of body weight, he became hypoxic, with a methemoglobin concentration of 12.2% (Table 1). He subsequently had acute intravascular hemolysis, with the hemoglobin level decreasing from 13.1 to 4.5 g per deciliter, the lactate dehydrogenase level increasing from 158 to 1229 U per liter, and the haptoglobin level decreasing from 130 to 10 mg per deciliter. An elevated plasma oxyhemoglobin level (30.9 mg per deciliter [4.8 μmol per liter]; reference range, 0.0 to 12.4 mg per deciliter [0.0 to 1.9 μmol per liter]) was accompanied by acute pulmonary hypertension (tricuspid regurgitant jet velocity of 3.5 m per second; reference range, 1.7 to 2.8).1,2 He was found to have a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Rasburicase causes oxidative stress by releasing hydrogen peroxide during the conversion of uric acid to allantoin.3 Although not specifically mentioned in the review by Howard et al. (May 12 issue),4 the Food and Drug Administration recommends that patients from populations where G6PD deficiency is common undergo testing before treatment with rasburicase.5 Table 1 Biochemical Evidence of Methemoglobinemia and Intravascular Hemolysis after Rasburicase Administration.*

Risk of acquired methemoglobinemia with different topical anesthetics during endoscopic procedures

IntroductionMethemoglobinemia is a recognized complication of the use of topical anesthetic sprays. The true scope of the problem or the risk with different topical anesthetic sprays and endoscopic procedures is unknown.MethodsWe retrospectively identified all cases of methemoglobinemia that occurred in a university affiliated community hospital from 2001 to 2007.ResultsEleven cases of methemoglobinemia were identified over the 6-year period. Nine (82%) occurred with use of benzocaine spray during transesophageal echocardiography (TEE). Patients who developed methemoglobinemia secondary to the topical anesthetic spray compared to other causes were more likely to be older, have lower mean hemoglobin levels (10.5 ± 0.5 g/dL vs 11.3 ± 0.0 g/dL), and a higher mean methemoglobin concentration at diagnosis (40.8% ± 5.2% vs 24% ± 10%). However, only age reached statistical significance (P = 0.004).ConclusionIn a university-affiliated community hospital, topical anesthetic sprays account for most of the burden of methemoglobinemia. Benzocaine use in the context of TEE caused more methemoglobinemia compared to lidocaine and other endoscopic procedures. This observation supports previous data and findings deserve further study.

Copper Pellets Simulating Oral Exposure to Copper Ammunition: Absence of Toxicity in American Kestrels (Falco sparverius)

To evaluate the potential toxicity of copper (Cu) in raptors that may consume Cu bullets, shotgun pellets containing Cu, or Cu fragments as they feed on wildlife carcasses, we studied the effects of metallic Cu exposure in a surrogate, the American kestrel (Falco sparverius). Sixteen kestrels were orally administered 5mg Cu/g body mass in the form of Cu pellets (1.18-2.00mm in diameter) nine times during 38days and 10 controls were sham gavaged on the same schedule. With one exception, all birds retained the pellets for at least 1h, but most (69%) regurgitated pellets during a 12-h monitoring period. Hepatic Cu concentrations were greater in kestrels administered Cu than in controls, but there was no difference in Cu concentrations in the blood between treated and control birds. Concentration of the metal-binding protein metallothionein was greater in male birds that received Cu than in controls, whereas concentrations in female birds that received Cu were similar to control female birds. Hepatic Cu and metallothionein concentrations in kestrels were significantly correlated. Histopathologic alterations were noted in the pancreas of four treated kestrels and two controls, but these changes were not associated with hepatic or renal Cu concentrations, and no lesions were seen in other tissues. No clinical signs were observed, and there was no treatment effect on body mass; concentrations of Cu, hemoglobin, or methemoglobin in the blood; or Cu concentrations in kidney, plasma biochemistries, or hematocrit. Based on the parameters we measured, ingested Cu pellets pose little threat to American kestrels (and presumably phylogenetically related species), although the retention time of pellets in the stomach was of relatively short duration. Birds expected to regurgitate Cu fragments with a frequency similar to kestrels are not likely to be adversely affected by Cu ingestion, but the results of our study do not completely rule out the potential for toxicity in species that might retain Cu fragments for a longer time.

Problems of haemoglobin freeze-drying: evidence that water removal is the key to iron oxidation.

Formation of methaemoglobin during freeze-drying of oxyhaemoglobin raises the question of the cause and mechanism of the oxidation. Haemoglobin with or without lyoprotector (250 mM glucose or amino acid salt) has been subjected to freeze drying changes in either or both of two constraints--vacuum and rise in temperature. A rise in temperature from -40 to +10 degrees C had no substantial denaturing effect on haemoglobin whether protected or not. Maintenance of a vacuum over frozen haemoglobin for 18 h often produced subtotal desiccation. Unprotected haemoglobin was partially oxidized (39% MetHb) whereas protected haemoglobin was not (less than 4% MetHb). Haemoglobin was also dried by rapid dehydration of thin films in a stream of air at room temperature (20 degrees C). The methaemoglobin content was then 43% whereas the amino acid salt or glucose limited it at 4 and 7%, respectively. Haemoglobin is oxidized, therefore, only because of the removal of water. Protectors, not specific in structure and action, probably work by holding or reinforcing the critical number of hydration layers around haemoglobin.

Toxische Methämoglobinämie

A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue.

Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial.

Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC). To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care. Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008. Intervention Inhaled nitric oxide gas vs inhaled nitrogen placebo. The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 cm or lower (on 0-10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home. There was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73.0 hours (95% confidence interval [CI], 46.0-91.0) and 65.5 hours (95% CI, 48.1-84.0), respectively (P = .87). There were no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite. Among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution. clinicaltrials.gov Identifier: NCT00094887.

Reference values for methemoglobin concentrations in children

ObjectiveThe aim of this work was to establish reference values for methemoglobin levels in 6 to 10-year-old children.MethodsMethemoglobin concentrations were studied in clinically healthy children. The method for methemoglobin measurement used, neither uses highly toxic chemical compounds nor expensive enzymatic methods, thus it is feasible in the laboratory routine.ResultsThe results showed higher reference values for clinically healthy children (from 3.61 to 6.44%) than for adults (from 1.9 to 3.8%).ConclusionThe higher concentrations of methemoglobin in children may be explained by smaller amounts of soluble cofactor cytochrome b5 and reduced activity of the cytochrome b5 reductase enzyme in red blood cells which make children particularly susceptible to the development of methemoglobinemia. Methemoglobin concentrations in children are higher than in normal adult subjects thus, adult reference values cannot be used to interpret infant methemoglobinemia.

Methaemoglobinemia Induced by MDMA?

Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO2) of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy). Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O2 binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O2. Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O2, and to observe the patient.

Methaemoglobin Content and NADH-methaemoglobin Reductase Activity of Three Human Erythrocyte Genotypes

Background: To study methaemoglobin content and NADH-methaemoglobin reductase activity of three human erythrocyte genotypes (HbAA, HbAS and HbSS). Materials and Methods: Studies to ascertain methaemoglobin concentration and level of NADH-methaemoglobin reductase activity of three human erythrocyte genotypes (HbAA, HbAS and HbSS) were carried out in forty-three (43) healthy male participants of confirmed erythrocyte genotypes: HbAA (N=15), HbAS (N=15) and HbSS (N=13). Spectrophotometric method was used for determination of the two erythrocyte parameters. Results: Whereas methaemoglobin concentrations in the three erythrocyte genotypes was in the order: HbAS 0.05) in methaemoglobin concentration and NADH-methaemoglobin reductase activity between HbAA and HbAS erythrocytes. Conclusion: The results showed a relationship between erythrocyte NADH-methaemoglobin reductase activity and methaemoglobin concentration.

Influence of high dose tumescent local anaesthesia with prilocaine on systemic interleukin (IL)‐6, IL‐8 and tumour necrosis factor‐α

Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-α levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880-4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 μg/mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U/L) 12 h after TLA application. TNF-α and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-α because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg/kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia.

Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis

Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in patients with sickle cell disease (SCD). The beneficial therapeutic effects of inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether NO breathing reduces acute VOC pain in adult patients and to study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were enrolled. After randomization but before treatment, five were found to not meet final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm) and nine to placebo (21% O2). Primary outcome was the mean change in pain scores after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both groups had similar baseline VAS pain scores but inhaled NO significantly reduced pain scores compared with placebo (P 5 0.02) at the end of NO inhalation. Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr. Parenteral morphine use was lower in the inhaled NO group, but the difference was not statistically significant.Safety assessments included systolic blood pressure measurements,pulse oximetry readings, concentration of delivered nitrogen dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities was observed.

Investigation on the Methaemoglobin Concentration of Three Human Erythrocyte Genotypes Infected With <i>Plasmodium falciparum</i>.

Investigation to ascertain the levels of methaemoglobin concentration of three human erythrocyte genotypes (HbAA, HbAS and HbSS) obtained from apparently healthy and clinically confirmed malarioussubjects/volunteers was carried out. Spectrophotometric method was used for the determination of erythrocyte methaemoglobin concentration. The mean (+S.D) methaemoglobin concentration, expressed as percentage (Met.Hb %) of total haemoglobin concentration of three erythrocyte was in the order: HbAA

Four-week oral toxicity study of three metabolites of nitrobenzene in rats

Our previous studies have shown that major metabolites of nitrobenzene in bovine and fowl were p-nitrophenol, p-aminophenol, and p-nitroaniline. There are few reports about the subacute toxicity of the three metabolites. The aim of this study was to investigate the subacute toxicity of these compounds. A suspension containing three metabolites at 50, 25, and 5 mg kg−1 body weight was administrated introgastrically to Sprague-Dawley rats of both sexes for 4 weeks. All four groups survived to the end of the 4-week treatment period. Compared to the control group, there was a significant difference in body-weight increases in rats administered nitrobenzene metabolites at 50 and 25 mg kg−1 (P < 0.01). ALT, AST, ALP, T-CHO, TP, albumin, and creatinine were significantly increased in the 50-mg kg−1 group and tended to increase in the 25-mg kg−1 group, compared with controls. There was no significant difference in glucose between treatment groups and controls. RBC counts and concentration of Hb decreased significantly in the 50- and 25-mg kg−1 groups, compared with controls, whereas WBC and Ret counts increased in the 50- and 25-mg kg−1 groups and LYM only in the 50-mg kg−1 group. There were no significant differences in MONO and neutrophil counts, compared with controls. Methemoglobin concentrations were significantly increased on day 21 of treatment in the 50-mg kg−1 group and on day 28 in the 25- and 50-mg kg−1 groups. The subacute toxicity was characterized by lesions affecting the liver, kidneys, spleen, cerebellum, and hematopoietic system.

Sub-chronic effects of nitrate in drinking water on red-legged partridge (Alectoris rufa): Oxidative stress and T-cell mediated immune function

In order to evaluate the effects of nitrates on birds, we have exposed captive red-legged partridges to nitrates concentrations of 0 (control), 100 (dwell water in farming areas) or 500 mg/l (fertirrigation level). The cellular immune response, plasma biochemistry, methemoglobin concentration (metHb), and oxidative stress biomarkers in blood and tissues were studied after two weeks of exposure. Several blood parameters such as aspartate aminotransferase, creatinine phosphokinase and lactate dehydrogenase activities and magnesium level decreased with nitrate exposure, whereas alkaline phosphatase activity and creatinine level increased. The oxidant effect of nitrates was evidenced by the increase in blood metHb, accompanied by the lipid peroxidation of red blood cells, the increased levels of oxidized glutathione (GSH) in liver, and the generation of oxidative DNA damage in plasma lymphocytes. GSH in erythrocytes was negatively correlated with blood metHb. The cellular immune function was slightly lower at partridges exposed to nitrates. These results suggest that adverse effects of nitrates on birds occur at concentrations potentially present in the field.

Index of Suspicion

Index of Suspicion