sodium-nitrite and Methemoglobinemia

Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths.. A systematic literature search was carried out on PubMed by following the PRISMA statement's criteria. A total of 35 studies with 132 cases were enrolled, and the data were cataloged in Microsoft Excel. To establish the causal correlation between sodium nitrite ingestion and death, the Naranjo Adverse Drug Reaction Probability Scale was used.. In addition to the small number of cases that have currently been published, the study demonstrated that there was a general methodological discrepancy in the diagnostic process. However, some interesting results have emerged, especially in post-mortem diagnostics.. Sodium-nitrite-related deaths represent a challenge for forensic pathologists; therefore, it is important to promptly recognize the essential features and perform the necessary and unrepeatable examinations for the correct diagnosis of the cause of death.

Topics: Cyanosis; Humans; Methemoglobinemia; Sodium; Sodium Nitrite; Suicide

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperbaric Oxygenation; Lacquer; Male; Methemoglobinemia; Middle Aged; Nitrites; Paint; Sodium Nitrite

To determine whether sodium thiosulfate (STS) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in an in-vitro model.. This was an in-vitro, controlled study where methemoglobinemia was induced by the addition of sodium nitrite (0.4 mg/mL) to 35-mL aliquots of blood obtained from ten healthy volunteers. Methemoglobin (MetHb) concentrations were measured at 5-minute intervals for 30 minutes by co-oximetry, and each aliquot was then subdivided into six 5-mL samples (time zero). Sample 1 served as control. The remaining samples received serial dilutions of STS (0.125 mg, 1.25 mg, 12.5 mg, 125 mg, 1,250 mg). MetHb concentrations were measured by co-oximetry at baseline, 0, 15, 30, 45, and 60 minutes. Areas under the MetHb concentration-time curve (AUC) between time zero and 60 minutes were compared using the Kruskal-Wallis test.. Methemoglobin concentrations increased from 0.07 g/dL (+/-0.06) at baseline to 8.42 g/dL (+/-0.69) at time 0 (the addition of STS). No significant difference was detected between baseline and time 0 hemoglobin concentrations (15.8 +/- 0.5 vs. 16.1 +/- 0.6 g/dL). There was no detectable difference found between the AUCs (measured in g min/dL) of any of the STS serial dilutions or control groups (0.125 mg STS = 576.01 +/- 42.53; 1.25 mg STS = 573.47 +/- 40.82; 12.5 mg STS = 583.68 +/- 42.29; 125 mg STS = 554.75 +/- 42.68; 1,250 mg STS = 566.95 +/- 38.08; p = 0.81).. Sodium thiosulfate was not found to be an effective reducing agent for the acute treatment of methemoglobinemia.

Topics: Antioxidants; Area Under Curve; Humans; In Vitro Techniques; Methemoglobinemia; Prospective Studies; Sodium Nitrite; Thiosulfates

To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers.. We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test.. There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM; P =.31). Mean AUC for the control group (77.1+/-5.7 g x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01).. Intravenous NAC failed to enhance methemoglobin reduction in this model.

Topics: Acetylcysteine; Adult; Area Under Curve; Cross-Over Studies; Free Radical Scavengers; Humans; Indicators and Reagents; Infusions, Intravenous; Male; Methemoglobin; Methemoglobinemia; Sodium Nitrite; Treatment Failure

The intentional ingestion of sodium nitrite causes toxicity by inducing methemoglobinemia, which can lead to cyanosis, hypotension and death. The number of reported suicide cases has significantly increased in the past 10 years as sodium nitrite is readily available online. The traditional tests for nitrite and nitrate require specialized detection methods which are not typically available in a postmortem toxicology laboratory. This rise in sodium nitrite overdose cases indicates the need for a simple, quick test for suspected nitrite toxicity. In this study, a common Griess reagent color test (MQuant™ Nitrite Test Strips) was used as a presumptive method in cases where the ingestion of sodium nitrite was suspected. The test results were consistent between specimens in all cases, and vitreous humor was identified as a reliable matrix to be used in the cases of suspected sodium nitrite poisonings. Case reports of five patients who died of suicide by sodium nitrite in a 6-month span are presented.

Topics: Humans; Methemoglobinemia; Nitrates; Sodium Nitrite; Suicide

An increase in suicide cases by sodium nitrate and sodium nitrite ingestion has been noted in the scientific literature. We report on the possible impact of nitrate/nitrite-caused methemoglobinemia on carboxyhemoglobin measurement by spectrophotometric methods. Elevated methemoglobin saturation may result in insufficient reducing agents to convert methemoglobin into deoxygenated hemoglobin, affecting the measured total hemoglobin and carboxyhemoglobin saturation. We highlight four cases where the cause of death was attributed to sodium nitrate or sodium nitrite ingestion. The possible impact of the nitrate/nitrite-caused methemoglobinemia on the carboxyhemoglobin saturation as measured by spectrophotometry is discussed. Further studies are needed to identify a causal relationship between nitrate/nitrite-caused methemoglobinemia and carboxyhemoglobin saturation as measured by spectrophotometric methods.

Topics: Carboxyhemoglobin; Humans; Methemoglobin; Methemoglobinemia; Nitrates; Sodium Nitrite

Topics: Humans; Methemoglobin; Methemoglobinemia; Nitrates; Sodium; Sodium Nitrite

Sodium nitrite intoxication reportedly causes severe methemoglobinemia. Recent studies reported that most clinically significant cases resulted from intentional exposure in suicidal attempts. We describe 2 cases of severe methemoglobinemia secondary to intentional sodium nitrite intoxication in suicidal attempts.. A 26-year-old man and 20-year-old woman attempted suicide by taking sodium nitrite, and were brought to the emergency department.. The male patient collapsed at the scene. He ingested approximately 18 g of sodium nitrate, and his methemoglobin level was 90.3%. The female patient was conscious, but was cyanotic. She ingested approximately 12.5 g of sodium nitrite, and her methemoglobin level was 54.6%.. The male patient received advanced cardiac life support in the emergency department. Methylene blue was immediately administered for the female patient.. The male patient died despite aggressive resuscitation. The female patient's cyanosis resolved, and her methemoglobin level decreased to 1.2% 3 hours later.. The immediate administration of methylene blue in severe methemoglobinemia patients prevented fatal consequences. The public should be informed about the accessibility and toxicity of sodium nitrite.

Topics: Cyanosis; Female; Humans; Male; Methemoglobinemia; Methylene Blue; Sodium Nitrite

Methemoglobinemia is the result of inappropriate oxidation of hemoglobin iron groups, leading to a failure of oxygen transport and delivery, resulting in a clinical state of refractory hypoxia. Methemoglobin levels above 70% are often considered fatal. Acquired methemoglobinemia can be caused by a variety of substances, including sodium nitrite, a commercially available food preservative and color fixative. This report describes a patient presenting with a methemoglobin level of 83% secondary to intentional sodium nitrite ingestion. The methemoglobin level recorded is amongst some of the highest found in surviving patients.

Topics: Child; Eating; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue; Sodium Nitrite

Sodium nitrite is a potent oxidizing agent that impairs oxygen transport and delivery through methemoglobin formation. Clinical manifestations are known to induce methemoglobinemia, dysrhythmia, hypotension, and even death. While accidental intoxication of sodium nitrite by contaminated water and food has previously occurred, there has been a substantial upsurge in suicide intoxication in recent years.. We present case reports of 2 patients who attempted suicide by sodium nitrite after ordering a "suicide powder" on the internet market. They were brought to the emergency department after attempting suicide by ingesting sodium nitrite. They experienced dyspnea, cyanosis, and mild nausea.. Based on their history and blood tests, methemoglobinemia was initially diagnosed.. The patients received methylene blue antidotal therapy in the emergency department. The patients were discharged after neuropsychiatric evaluation and treatment for mental illness, suicidal ideation, and suicide attempts. They informed us of how simple and easy it was for them to buy sodium nitrite for suicidal purposes.. With widely shared information on the usage of sodium nitrite for suicide and the absence of proper regulation, the incidence of acute poisoning will increase. This increases physicians' chances of encountering unexplained cyanosis and methemoglobinemia. Clinical suspicion of sodium nitrite intoxication is warranted in cases of unexplained cyanosis or methemoglobinemia. We want to highlight how simple and easy it is to buy sodium nitrite for suicidal purposes.

Topics: Cyanosis; Humans; Internet; Methemoglobinemia; Methylene Blue; Sodium Nitrite; Suicide, Attempted

Topics: Drug Overdose; Humans; Methemoglobinemia; Sodium Nitrite

Topics: Abdominal Injuries; Burns; Burns, Chemical; Eating; Humans; Methemoglobinemia; Sodium Nitrite; Thoracic Injuries

Sodium nitrite (NaNO

Topics: Eating; Fertilizers; Food Additives; Forensic Pathology; Heme; Hemoglobins; Humans; Hypoxia; Iron; Methemoglobin; Methemoglobinemia; Sodium Nitrite; Suicidal Ideation

Topics: Eating; Humans; Methemoglobinemia; Poisoning; Sodium Nitrite; Suicide

Topics: France; Humans; Methemoglobinemia; Sodium; Sodium Nitrite

Topics: Adult; Eating; Emergency Service, Hospital; Enzyme Inhibitors; Female; Food Additives; Humans; Methemoglobinemia; Methylene Blue; Sodium Nitrite; Treatment Outcome

Intramuscular (IM) injection of nitrite (1-10 mg/kg) confers survival benefit and protects against lung injury after exposure to chlorine gas in preclinical models. Herein, we evaluated safety/toxicity parameters after single, and repeated (once daily for 7 days) IM injection of nitrite in male and female Sprague Dawley rats and Beagle dogs. The repeat dose studies were performed in compliance with the Federal Drug Administration's (FDA) Good Laboratory Practices Code of Federal Regulations (21 CFR Part 58). Parameters evaluated consisted of survival, clinical observations, body weights, clinical pathology, plasma drug levels, methemoglobin and macroscopic and microscopic pathology. In rats and dogs, single doses of ≥100 mg/kg and 60 mg/kg resulted in death and moribundity, while repeated administration of ≤30 or ≤ 10 mg/kg/day, respectively, was well tolerated. Therefore, the maximum tolerated dose following repeated administration in rats and dogs were determined to be 30 mg/kg/day and 10 mg/kg/day, respectively. Effects at doses below the maximum tolerated dose (MTD) were limited to emesis (in dogs only) and methemoglobinemia (in both species) with clinical signs (e.g. blue discoloration of lips) being dose-dependent, transient and reversible. These signs were not considered adverse, therefore the No Observed Adverse Effect Level (NOAEL) for both rats and dogs was 10 mg/kg/day in males (highest dose tested for dogs), and 3 mg/kg/day in females. Toxicokinetic assessment of plasma nitrite showed no difference between male and females, with C

Topics: Animals; Antidotes; Dogs; Dose-Response Relationship, Drug; Female; Injections, Intramuscular; Male; Maximum Tolerated Dose; Methemoglobinemia; No-Observed-Adverse-Effect Level; Rats, Sprague-Dawley; Risk Assessment; Sex Factors; Sodium Nitrite; Species Specificity; Toxicity Tests; Toxicokinetics; Vomiting

Nitrites are chemicals that are abundant in the environment, widely used as preservatives for meat, and in pharmaceuticals. Volatile products containing nitrites have been used recreationally for the euphoric effect associated with mild hypoxia. Dietary exposure to small amounts is considered harmless. Deaths by ingestion of nitrite salts are not common, but accidental exposure and as suicidal and homicidal agents have been noted. Death is a consequence of oxidation of hemoglobin ferrous (Fe

Topics: Female; Food Preservatives; Humans; Kidney; Male; Methemoglobinemia; Middle Aged; Myocardium; Sodium Nitrite; Suicide, Completed; Young Adult

Topics: Eating; Humans; Methemoglobinemia; Sodium Nitrite; Suicide, Attempted

Topics: Humans; Methemoglobinemia; Sodium Nitrite; Suicidal Ideation

The use of sodium nitrite in suicide has become more common among young adults in the Republic of Korea. This report details the case of a 28-year-old man; the man had posted on a social network service detailing his attempt at suicide at 13:45. In the posted article, he stated that he had ingested 84 g of sodium nitrite. A post-mortem (PM) inspection was performed at 21:00, and peripheral blood (PB) was collected. An autopsy was performed approximately 44 h after death. The victim's face was dark brown in color, but the color of his oral mucosa was bright red. Toxicological analyses revealed 33% and 26% methemoglobinemia in the PB collected during PM inspection and autopsy, respectively. The concentration of nitrate in the PB collected during PM inspection, and PB and cardiac blood collected during the autopsy were 220.6 mg/L, 220.0 mg/L, and 218.5 mg/L, respectively. Nitrate was also detected in the pericardial fluid and cerebrospinal fluid at levels of 91.7 mg/L and 50.5 mg/L, respectively. The cause of death was determined to be methemoglobinemia-induced hypoxia due to sodium nitrite ingestion. This intoxication case informs some novel points about nitrite intoxication; the concentration of methemoglobin decreased during the PM period, while the concentration of nitrate was stable. There was no difference in the concentration of nitrate between cardiac and peripheral blood. Nitrate could be detected in the pericardial fluid and cerebrospinal fluid. This new information is helpful for better identifying future cases of nitrite intoxication.

Topics: Adult; Autopsy; Heart; Humans; Male; Methemoglobinemia; Republic of Korea; Sodium Nitrite; Young Adult

We report a case of fatal methaemoglobinaema resulting from sodium nitrite poisoning. A 28 year old woman arrested in the emergency department following collapse. During resuscitation a venous blood gas revealed a methaemoglobin percentage of 81%. Following treatment with methylene blue, sodium bicarbonate and adrenaline, the methaemoglobin decreased. Prior to transfer to intensive care, a CT head revealed extensive hypoxic brain injury. Two days later brain death was confirmed on brainstem testing. Severe methaemoglobinaemia is rapidly fatal, with fast diagnosis and treatment associated with improved outcomes.

Topics: Adult; Female; Humans; Methemoglobinemia; Methylene Blue; Sodium; Sodium Nitrite

Topics: Adult; Aged; Aged, 80 and over; Blood; Female; Heart; Humans; Magnetic Resonance Imaging; Male; Methemoglobinemia; Middle Aged; Nitrates; Skin Pigmentation; Sodium Nitrite; Suicide, Completed; Young Adult

Fatal sodium nitrite poisonings are unusual in the forensic setting. Suicide by poisoning includes drug overdose, the inhalation of toxic gasses, and poisoning from pesticides and chemical substances. Sodium nitrite is an inorganic compound usually seen as a crystalline powder that is very water soluble. Sodium nitrite is used mostly in the food industry (as a preservative) and in medical field (as an antidote to cyanide poisoning), and if ingested in large enough amounts, it can be fatal.The ingestion of sodium nitrite can cause severe methemoglobinemia, which is a metabolic disorder characterized by an inability of hemoglobin (which gets oxidized into methemoglobin) to bind (and therefore carry) oxygen. Severe cases of this condition, if not treated, can be fatal.We describe a case of fatal self-poisoning with sodium nitrite; in particular, the article focuses on the autoptic and toxicological investigations that enabled the correct diagnosis to be established.

Topics: Autopsy; Humans; Methemoglobin; Methemoglobinemia; Sodium Nitrite

Sodium nitrite is known to induce methemoglobinemia and hypotension when ingested, but reports of intentional ingestion remain rare.. We report five cases of severe methemoglobinemia secondary to large sodium nitrite ingestion that were reported to and managed by the California Poison Control System in 2019, resulting in three fatalities. The estimated doses ingested ranged from 15 grams to 113 grams, with one patient surviving after an ingestion of 60 grams. The highest documented methemoglobin level was 73%. The 2 patients who survived received methylene blue early in their clinical course. One patient required higher doses of methylene blue compared with other cases of nitrite-associated methemoglobinemia. In the patients who survived, all symptoms resolved within 24 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These cases highlight the severe toxicity associated with intentional large sodium nitrite ingestion. In management, consideration should be given to administering higher initial or more frequent doses of methylene blue compared with standard practice. Given that sodium nitrite is readily accessible through online vendors, and is being circulated through various suicide forums, it has the potential to be more commonly encountered in the emergency department.

Topics: Eating; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue; Sodium Nitrite

Sodium nitrite is used as a coloring agent or preservative in food, as well as an antimicrobial agent in meat and fish and some cheeses. In high amounts it can be toxic for humans, causing methemoglobinemia. This is an unusual and potentially fatal condition in which hemoglobin is oxidized to methemoglobin (MHb), reducing the amount of oxygen that is released from hemoglobin, similar to carbon monoxide poisoning. MHb levels of 70% are generally lethal, but the existence of underlying anemia, acidosis, respiratory compromise, and cardiac disease may exacerbate the toxicity of MHb. We present a case of poisoning with sodium nitrite in three family members after eating homemade sausages given to them by their neighbor who was a butcher. According to the findings of the veterinary inspectorate in charge of food control in this case, the concentration of sodium nitrite in the homemade sausages was about 3.5 g per 1 kg of meat, almost 30 times higher than allowed according to legislation. In this case report, a 70-year-old man died about 7 h after consuming the meal, while two women, 53 and 67 years of age, respectively, were admitted to a toxicology clinic the following day due to food poisoning, with the maximum concentration of MHb in blood of 33.7 and 20.4%, respectively. They were discharged 3 days later. The autopsy of the deceased man showed sodium nitrite poisoning with a relatively low concentration of MHb in his blood - 9.87%. Death was attributed to the exacerbation of hypertensive and ischemic heart disease, resulting from accidental sodium nitrite poisoning. The presented cases illustrate the necessity of close cooperation between the authorities, medical staff, veterinary inspectorate, and forensic pathologists in determining the source of poisoning, the cause of death of the victim, and preventing the outbreak of poisoning among a greater number of consumers.

Topics: Accidents, Home; Aged; Female; Food Preservatives; Foodborne Diseases; Humans; Hypertension; Male; Meat Products; Methemoglobinemia; Middle Aged; Myocardial Ischemia; Sodium Nitrite

We present two patients who were treated for an intentional overdose of sodium nitrite. When ingested sodium nitrite leads to severe methaemoglobinaemia, resulting in severe hypoxia (as methaemoglobin does not transport oxygen), vasodilation and hypotension. Symptoms include cyanosis, headache, nausea, convulsions, coma and death. When measured by pulse oximetry, patients with a sodium nitrite intoxication and severe methaemoglobinaemia generally have an oxygen saturation of around 85%. This value is unreliable as the oxygen content of the blood is often extremely low - this can be confirmed by arterial blood gas analysis. Treatment of sodium nitrite intoxication consists of intravenous administration of methylthioninium chloride 1-2 mg/kg. Methylthioninium chloride converts the methaemoglobin back to haemoglobin. Due to the pharmacokinetics of methylthioninium chloride and sodium nitrite, a rebound effect is not to be expected. The only contra-indication for methylthioninium chloride is glucose-6-phosphate dehydrogenase deficiency, which is extremely rare in the Netherlands.

Topics: Adult; Drug Overdose; Enzyme Inhibitors; Food Preservatives; Humans; Hypoxia; Male; Methemoglobinemia; Methylene Blue; Oxygen; Poisoning; Sodium Nitrite; Suicide, Attempted

Topics: Aged; Blood Gas Analysis; Fatal Outcome; Female; Food Contamination; Humans; Male; Mass Casualty Incidents; Methemoglobinemia; Middle Aged; Ships; Sodium Nitrite; Vital Signs

Topics: Ethylene Glycol; Humans; Male; Methemoglobinemia; Methylene Blue; Middle Aged; Sodium Nitrite; Suicide, Attempted

Topics: Animals; Female; Fishes; Food Contamination; Foodborne Diseases; Humans; Methemoglobinemia; Middle Aged; Sodium Nitrite

Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents.. We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents.. A retrospective case-control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included.. Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p = 0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p = 0.001, 455 mg vs. 144 mg, p = 0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72 h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia.. The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Dapsone; Dose-Response Relationship, Drug; Drug Overdose; Emergency Service, Hospital; Female; Humans; Lidocaine; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Middle Aged; Oxazines; Poisoning; Primaquine; Retrospective Studies; Sodium Nitrite; Treatment Outcome; Young Adult

A major concern during pesticide development and use is the impact on non-target species, such as raptors or domestic cats and dogs. Sodium nitrite and para-aminopropiophenone (PAPP) are two toxicants currently being studied for the control of invasive species, such as starlings and feral swine. When given to an animal these compounds oxidize hemoglobin, which renders it unable to carry oxygen resulting in methemoglobinemia. This study developed a method to estimate methemoglobin levels in mammals and birds by examining the efficacy of sodium nitrite to induce the conversion of hemoglobin to methemoglobin. Varying concentrations of sodium nitrite were added to aliquots of coyote, vole, feral swine, starling, and duck blood, collected from captive animals. The blood samples were analyzed spectrophotometrically to determine percent methemoglobin and digitally to determine red color values (RCV) associated with different methemoglobin levels. The avian and mammalian blood reached 100% methemoglobin levels at 200 mM and 15 mM sodium nitrite, respectively. All animals had similar RCV for a given percent methemoglobin. In conclusion, this study developed a procedure to quickly determine methemoglobin levels in mammals and birds. Furthermore, percent methemoglobin can be estimated with one standard curve from any animal species and an image of a blood spot. The technique will be useful during field studies, in agricultural areas, or in a veterinarian's office for the rapid diagnosis of methemoglobinemia in non-target animals that have eaten toxicants/baits or baited animals.

Topics: Animals; Animals, Wild; Arvicolinae; Bird Diseases; Colorimetry; Coyotes; Ducks; Methemoglobin; Methemoglobinemia; Sodium Nitrite; Spectrophotometry; Starlings; Swine; Swine Diseases

Acute mountain sickness, one of the most common altitude diseases, causes lung and brain injury. The present study aimed to investigate the anti‑hypoxic effect of purified polysaccharides extracted from Cordyceps militaris. The aqueous extract of Cordyceps militaris was purified progressively through a DEAE‑52 cellulose anion exchange column and a Sepharose G‑100 column. The fraction CMN1, with a molecular weight of 37842 Da, was the main fraction obtained and its chemical composition and structural characteristics were determined. CMN1 was found to have a monosaccharide composition of L‑rhamnose, L‑arabinose, D‑mannose, D‑galactose. The backbone of CMN1 comprised (1→2) and (1→3) linkages, with branched (1→6) and (1→4) linkages. The anti‑hypoxic effects of CMN1 were determined using a sodium nitrite toxicosis test, acute cerebral ischemic/hypoxic test and normobarie hypoxia test. CMN1 (0.5 g/kg) possessed a similar anti‑hypoxic effect to rhodiola oral liquid. Overall, the Cordyceps militaris polysaccharide, CMN1, was identified as an effective agent against hypoxia.

Topics: Animals; Apoptosis; Chromatography, Gel; Chromatography, Ion Exchange; Cordyceps; Female; Hypoxia; Male; Methemoglobinemia; Mice; Molecular Weight; Polysaccharides; Sodium Nitrite; Spectroscopy, Fourier Transform Infrared; Survival Rate

There are currently no FDA-approved antidotes for H2S/sulfide intoxication. Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be highly protective against the acute toxic effects of sodium hydrosulfide (∼LD40 dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toxicant dose did not detectably ameliorate sulfide toxicity in this fast-delivery, single-shot experimental paradigm. Nitrite anion was shown to rapidly produce NO in the bloodstream, as judged by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin, together amounting to less than 5% of the total hemoglobin present. Sulfide-intoxicated mice were neither helped by the supplemental administration of 100% oxygen nor were there any detrimental effects. Compared to cyanide-intoxicated mice, animals surviving sulfide intoxication exhibited very short knockdown times (if any) and full recovery was extremely fast (∼15 min) irrespective of whether sodium nitrite was administered. Behavioral experiments testing the ability of mice to maintain balance on a rotating cylinder showed no motor impairment up to 24 h post sulfide exposure. It is argued that antagonism of sulfide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity of nitrite rather than formation of methemoglobin.

Topics: Animals; Anions; Antidotes; Cattle; Cell Line; Cyanides; Electron Spin Resonance Spectroscopy; Electron Transport Complex IV; Hemoglobins; Injections, Intraperitoneal; Male; Methemoglobin; Methemoglobinemia; Mice; Motor Activity; Muscle, Skeletal; Myocardium; Nitric Oxide; Sodium Nitrite; Sulfides

Construction workers are exposed to a wide variety of health hazards such as poisoning at the construction sites. Various forms of poisoning incidents in construction workers have been reported. However, studies on methemoglobinemia caused by unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites have not been reported yet.. The aim of this study was to evaluate life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites and describe similar incidents involving ingestion of antifreeze admixtures in Korea.. Retrospective observational case series study on patients with methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite admitted to the emergency department (ED) from January 1, 2010 to December 31, 2012 and cases reported to the Korea Occupational Safety and Health Agency (KOSHA) was performed. Results. Six victims were admitted to our ED. They had methemoglobin levels ranging from 32.4% to 71.5% and all of them recovered after receiving one (2 mg/kg) or two doses infusion of methylene blue. From the data of the KOSHA, six incidents that caused 27 victims were identified. Of 27 victims, five were included in the ED cases. For all incidents, antifreeze admixtures were not contained in their original containers and all new containers did not have a new label. All workers mistook antifreeze admixtures for water. Among the 28 victims included in this study, four died.. Unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites can cause life-threatening methemoglobinemia. There is a need to store and label potentially hazardous materials properly to avoid unintentional ingestion at the construction sites.

Topics: Accidents; Aged; Antidotes; Construction Industry; Humans; Intubation, Intratracheal; Male; Methemoglobinemia; Methylene Blue; Middle Aged; Occupational Exposure; Polyethylene Glycols; Republic of Korea; Retrospective Studies; Sodium Nitrite; Treatment Outcome

Historically, nitrogen oxides (NO

Topics: Administration, Inhalation; Animals; Animals, Inbred Strains; Antihypertensive Agents; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drugs, Investigational; Female; Hypertension, Pulmonary; Hypotension; Infusions, Intravenous; Male; Methemoglobinemia; Nasal Cavity; Nasal Mucosa; No-Observed-Adverse-Effect Level; Rats, Sprague-Dawley; Risk Assessment; Sodium Nitrite; Species Specificity; Toxicity Tests, Chronic

It was investigated the features of microcirculation and mechanisms it's conditioned, under acute administration of sodium nitrite in 5 mg of dry substance per 100 g of body weight. It was shown that acute administration of sodium nitrite leads to the development of methemoglobinemia, arterial and venous hypoxemia, and severe tissue hypoxia. Increase in the diffusion path O2 at methemoglobinemia is caused due to significant hyperhydratation of lung air-blood barrier and its individual layers, and is accompanied by a decrease in both components of the diffusion capacity of the lungs for oxygen: its membrane and blood components. It was revealed that the administration of sodium nitrite has a double effect, leading to inactivation of hemoglobin, as well as to microcirculatory disturbances associated primarily with changes in the regulation of vascular tone. In this initial perfusion per unit volume of tissue per time unit intrinsic for the organism defines a set of mechanisms which are responsible for changes in tissue blood flow under methemoglobinemia.

Topics: Animals; Blood Vessels; Blood-Air Barrier; Diffusion; Hypoxia; Lung; Male; Methemoglobinemia; Microcirculation; Oxygen; Rats; Sodium Nitrite; Water

Topics: Female; Food Preservatives; Humans; Methemoglobinemia; Middle Aged; Sodium Nitrite

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Topics: 4-Aminopyridine; Age Factors; Algorithms; Antidotes; Child; Child, Preschool; Cyanides; Disease Management; Disease Susceptibility; Emergencies; Emergency Medical Services; Europe; Fires; Humans; Hydroxocobalamin; Infant; Methemoglobinemia; Poisoning; Smoke; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

Methemoglobin in the blood cannot be detected by conventional pulse oximetry, although it can bias the oximeter's estimate (Spo2) of the true arterial functional oxygen saturation (Sao2). A recently introduced "Pulse CO-Oximeter" (Masimo Rainbow SET(R) Radical-7 Pulse CO-Oximeter, Masimo Corp., Irvine, CA) is intended to additionally monitor noninvasively the fractional carboxyhemoglobin and methemoglobin content in blood. The purpose of our study was to determine whether hypoxia affects the new device's estimated methemoglobin reading accuracy, and whether the presence of methemoglobin impairs the ability of the Radical-7 and a conventional pulse oximeter (Nonin 9700, Nonin Medical Inc., Plymouth, MN) to detect decreases in Sao2.. Eight and 6 healthy adults were included in 2 study groups, respectively, each fitted with multiple sensors and a radial arterial catheter for blood sampling. In the first group, IV administration of approximately 300 mg sodium nitrite increased subjects' methemoglobin level to a 7% to 8% target and hypoxia was induced to different levels of Sao2 (70%-100%) by varying fractional inspired oxygen. In the second group, 15% methemoglobin at room air and 80% Sao2 were targeted. Pulse CO-oximeter readings were compared with arterial blood values measured using a Radiometer multiwavelength hemoximeter. Pulse CO-oximeter methemoglobin reading performance was analyzed by observing the incidence of meaningful reading errors at the various hypoxia levels. This was used to determine the impact on predictive values for detecting methemoglobinemia. Spo2 reading bias, precision, and root mean square error were evaluated during conditions of elevated methemoglobin.. Observations spanned 66.2% to 99% Sao2 and 0.6% to 14.4% methemoglobin over the 2 groups (170 blood draws). Masimo methemoglobin reading bias and precision over the full Sao2 span was 7.7% +/- 13.0%. Best accuracy was found in the 95% to 100% Sao2 range (1.9% +/- 2.5%), progressing to its worst in the 70% to 80% range (24.8% +/- 15.6%). Occurrence of methemoglobin readings in error >5% increased over each 5-point decrease in Sao2 (P < 0.05). Masimo Spo2 readings were biased -6.3% +/- 3.0% in the 95% to 100% Sao2 range with 4% to 8.3% methemoglobin. Both the Radical-7 and Nonin 9700 pulse oximeters accurately detected decreases in Sao(2) <90% with 4% to 15% methemoglobin, despite displaying low Spo2 readings when Sao2 was >95%.. The Radical-7's methemoglobin readings become progressively more inaccurate as Sao2 decreases <95%, at times overestimating true values by 10% to 40%. Elevated methemoglobin causes the Spo2 readings to underestimate Sao2 similar to conventional 2-wavelength pulse oximeters at high saturation. Spo2 readings from both types of instruments continue to trend downward during the development of hypoxemia (Sao2 <90%) with methemoglobin levels up to 15%.

Topics: Adult; Blood Gas Analysis; Carbon Monoxide; Carboxyhemoglobin; Data Interpretation, Statistical; Female; Hemoglobinometry; Humans; Hypoxia; Male; Methemoglobin; Methemoglobinemia; Oximetry; Oxygen; Predictive Value of Tests; Reproducibility of Results; Sodium Nitrite

A 49-year-old man lost consciousness after being accidentally exposed to what was probably hydrogen sulfide gas while performing maintenance on a machine producing feather meal. He was immediately taken to the hospital. Upon admission, his consciousness level was 14 (E4V4M6) on the Glasgow Coma Scale (GCS), but it subsequently decreased, and the patient was intubated when his respirations became depressed as well. About 5 hours after the initial incident, he was transferred to our department. His consciousness level was GCS 9 (E2V2M5), his blood pressure was 95/78 mmHg, and his heart rate was 90 beats per min. There was no metabolic acidosis. Mechanical ventilation was begun and 10% sodium nitrite was intermittently administered intravenously, with the goal of lowering arterial blood methemoglobin saturation to 20%. Two days following admission, the patient regained full consciousness and sodium nitrite administration was stopped. The following day mechanical ventilation was also discontinued. This patient exhibited severe recurring neurologic symptoms without metabolic acidosis; thus, the manifestations of toxicity in this case might have been due to the direct neurologic toxicity of hydrogen sulfide, hypoxia, or delayed post-ischemic cerebral hypoperfusion syndrome. The patient made a full recovery without any sequelae; therefore we would like to hypothesize that repetitive intravenous administration of sodium nitrite is effective in cases of hydrogen sulfide exposure.

Topics: Accidents, Occupational; Acidosis; Gases; Humans; Hydrogen Sulfide; Infusions, Intravenous; Male; Methemoglobinemia; Middle Aged; Occupational Exposure; Respiration, Artificial; Sodium Nitrite; Treatment Outcome; Unconsciousness

We report the case of a patient suffering from a severe methemoglobinaemia following accidental sodium nitrite intoxication, a substance frequently used as a preservation agent for animal feed. On base of this case report, pathophysiology, clinical symptoms, diagnostical and therapeutical options with methylene blue (1-2 mg/kg of body weight) are discussed. Recently, pulse oximeters capable to measure 4 different hemoglobins have been introduced. These may be helpful for diagnosis especially in the prehospital setting.

Topics: Administration, Oral; Humans; Male; Methemoglobinemia; Methylene Blue; Sodium Nitrite

The objective of this study was to evaluate the effects of sodium nitrite (NaNO(2))-induced methemoglobinaemia on plasma ATP (adenosine triphosphate) and corresponding changes of blood-ionized magnesium (iMg(2+)) as well as total magnesium (tMg(2+)) in a time-dependent manner. This study was performed on male Sprague-Dawley rats to which NaNO(2) was injected (10 mg/kg i.p.) to induce methemoglobinaemia. Methemoglobin (MetHb) in blood was measured before (0 min.) and after 10, 30, 60 and 120 min. of NaNO(2) injection. At respective time points, the tMg(2+), blood ions and gases were measured by atomic absorption spectrometry and ion selective electrode, respectively. Haematological parameters were checked by automatic blood cell count, and blood films were observed under light microscope. Plasma ATP was measured by bioluminescence assay using a luminometer, and plasma proteins were measured by an automatic analyser. Blood cell count (RBC, WBC and platelet), haematocrit, and haemoglobin were found to be decreased with the advancement of MetHb concentration. With the gradual increase of MetHb concentration, the plasma ATP decreased and blood iMg(2+) and plasma tMg(2+) increased significantly as time passed by in comparison with the pre-drug values. A significant decrease of the ratio of ionized calcium to iMg(2+), Na(+) and increase of K(+) was observed. In conclusion, NaNO(2)-induced methemoglobinaemia is a cause of hydrolysis of plasma ATP which is responsible for the increase of blood iMg(2+) and plasma tMg(2+) in rats.

Topics: Adenosine Triphosphate; Animals; Calcium; Cations, Divalent; Hydrolysis; Injections, Intraperitoneal; Ion-Selective Electrodes; Magnesium; Male; Methemoglobin; Methemoglobinemia; Potassium; Rats; Rats, Sprague-Dawley; Sodium Nitrite; Spectrophotometry, Atomic

Five cases of methaemoglobinaemia after ingestion of sodium nitrite occurred in two clusters in Sydney in 2006. All cases were unintentional poisonings following use in cooking of an imported compound sold as a food additive. In all cases, methaemoglobinaemia was recognised early and treated promptly, with all patients making a full recovery. These cases highlight the importance of accurate food labelling and surveillance of imported goods.

Topics: Cyanosis; Enzyme Inhibitors; Female; Food Additives; Food Labeling; Humans; Male; Methemoglobinemia; Methylene Blue; Sodium Nitrite

One of the major obstacles hindering the clinical development of a cell-free, hemoglobin-based oxygen carrier (HBOC) is systemic vasoconstriction.. Experiments were performed in healthy mice and lambs by infusion of either murine tetrameric hemoglobin (0.48 g/kg) or glutaraldehyde-polymerized bovine hemoglobin (HBOC-201, 1.44 g/kg). We observed that intravenous infusion of either murine tetrameric hemoglobin or HBOC-201 induced prolonged systemic vasoconstriction in wild-type mice but not in mice congenitally deficient in endothelial nitric oxide (NO) synthase (NOS3). Treatment of wild-type mice by breathing NO at 80 ppm in air for 15 or 60 minutes or with 200 ppm NO for 7 minutes prevented the systemic hypertension induced by subsequent intravenous administration of murine tetrameric hemoglobin or HBOC-201 and did not result in conversion of plasma hemoglobin to methemoglobin. Intravenous administration of sodium nitrite (48 nmol) 5 minutes before infusion of murine tetrameric hemoglobin also prevented the development of systemic hypertension. In awake lambs, breathing NO at 80 ppm for 1 hour prevented the systemic hypertension caused by subsequent infusion of HBOC-201.. These findings demonstrate that HBOC can cause systemic vasoconstriction by scavenging NO produced by NOS3. Moreover, in 2 species, inhaled NO administered before the intravenous infusion of HBOC can prevent systemic vasoconstriction without causing methemoglobinemia.

Topics: Administration, Inhalation; Animals; Blood Substitutes; Blood Transfusion; Drug Evaluation, Preclinical; Hemodynamics; Hemoglobins; Hypertension; Infusions, Intravenous; Methemoglobinemia; Mice; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Premedication; Sheep; Sodium Nitrite; Vasoconstriction; Vasodilator Agents; Wakefulness

Topics: Antidotes; Documentation; Drug Approval; Emergency Service, Hospital; Humans; Informed Consent; Japan; Methemoglobinemia; Methylene Blue; Pharmacy Service, Hospital; Quality Control; Sodium Nitrite; Surveys and Questionnaires; Technology, Pharmaceutical

The reaction of nitrite with deoxyhemoglobin results in the production of nitric oxide and methemoglobin, a reaction recently proposed as an important oxygen-sensitive source of vasoactive nitric oxide during hypoxic and anoxic stress, with several animal studies suggesting that nitrite may have therapeutic potential. Accumulation of toxic levels of methemoglobin is suppressed by reductase enzymes present within the erythrocyte. Using a novel method of measuring methemoglobin reductase activity in intact erythrocytes, we compared fetal and adult sheep and human blood. After nitrite-induced production of 20% methemoglobin, the blood was equilibrated with carbon monoxide, which effectively stopped further production. Methemoglobin disappearance was first order in nature with specific rate constants (k x 1,000) of 12.9 +/- 1.3 min(-1) for fetal sheep, 5.88 +/- 0.26 min(-1) for adult sheep, 4.27 +/- 0.34 for adult humans, and 3.30 +/- 0.15 for newborn cord blood, all statistically different from one another. The effects of oxygen tensions, pH, hemolysis, and methylene blue are reported. Studies of temperature dependence indicated an activation energy of 8,620 +/- 1,060 calories/mol (2.06 kJ/mol), appreciably higher than would be characteristic of processes limited by passive membrane diffusion. In conclusion, the novel methodology permits absolute quantification of the reduction of nitrite-induced methemoglobin in whole blood.

Topics: Adult; Animals; Carbon Monoxide; Cytochrome-B(5) Reductase; Drug Combinations; Fetal Blood; Humans; Indicators and Reagents; Infant, Newborn; Methemoglobin; Methemoglobinemia; Oxidation-Reduction; Reproducibility of Results; Sheep; Sodium Nitrite

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 microM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.

Topics: Animals; Disease Models, Animal; Hemoglobins; Kinetics; Methemoglobin; Methemoglobinemia; Methylene Blue; Oxidation-Reduction; Oxyhemoglobins; Photons; Rabbits; Scattering, Radiation; Sodium Nitrite; Spectroscopy, Near-Infrared

Topics: Aged; Humans; Male; Methemoglobinemia; Sodium Chloride, Dietary; Sodium Nitrite

Topics: Enzyme Inhibitors; Food Contamination; Humans; Male; Meat Products; Methemoglobinemia; Methylene Blue; Middle Aged; Sodium Nitrite; Treatment Outcome

A 22-year-old woman with an initial diagnosis of 'ruptured ectopic pregnancy' and 'hemorrhagic shock' was sent to the operation room for surgical treatment. The mucocutaneous color was deeply cyanosed and the pulse oximeter oxygen saturation (SpO2) was only 86% after tracheal intubation (100% O2). 'Chocolate-brown' blood was observed and methemoglobinemia was considered. Then the arterial blood gas (ABG) sample was obtained, an intravenous infusion of methylene blue and vitamin C followed. The patient recovered quickly, and later two other patients with similar symptoms were treated in the same way. The success was due to a correct diagnosis accompanied with prompt treatment and quick recognition of the etiology.

Topics: Adult; Antidotes; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Diagnosis, Differential; Female; Food Preservatives; Humans; Meat; Methemoglobinemia; Methylene Blue; Nitrates; Oxygen; Pregnancy; Pregnancy, Ectopic; Rupture; Shock, Hemorrhagic; Sodium Nitrite

Methemoglobinemia is an unusual and potentially fatal condition in which hemoglobin is oxidized to methemoglobin and loses its ability to bind and transport oxygen. The most common cause of methemoglobinemia is the ingestion or inhalation of oxidizing agents such as nitrates or nitrites (e.g., sodium nitrite, which is used commonly as a preservative in curing meats and fish). This report summarizes the investigation of an incident of methemoglobinemia in five members of a household in New York who became ill after eating a meal seasoned with a white crystalline substance from a plastic bag labeled "Refined Iodized Table Salt" (Figure). The findings underscore the need for proper storage of hazardous materials to avoid unintentional ingestion and the importance of collaboration by multiple agencies to address a potential public health emergency.

Topics: Adult; Cyanosis; Dizziness; Enzyme Inhibitors; Female; Food Labeling; Food Preservatives; Humans; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Middle Aged; New York; Respiratory Insufficiency; Seizures; Sodium Chloride, Dietary; Sodium Nitrite; Unconsciousness; Vomiting

A biologically based mathematical model was created to characterize time and dose-dependent relationships between exposure to nitrite and induction of methemoglobinemia. The model includes mass action equations for processes known to occur: oral absorption of nitrite, elimination from the plasma, partitioning between plasma and erythrocytes, binding of nitrite to hemoglobin and methemoglobin, and the free radical chain reaction for hemoglobin oxidation. The model also includes Michaelis-Menten kinetics for methemoglobin reductase-catalyzed regeneration of hemoglobin. Body weight-scaled rate constants for absorption (k(a)) and elimination (k(e)), the effective erythrocyte/plasma partition coefficient (P), and the apparent K(m) for methemoglobin reductase were the only parameters estimated by formal optimization to reproduce the observed time course data. Time courses of plasma nitrite concentrations and blood levels of hemoglobin and methemoglobin in male and female rats that had received single intravenous or oral doses of sodium nitrite were measured. Peak plasma levels of nitrite were achieved in both sexes approximately 30 min after oral exposure, and peak methemoglobin levels were achieved after 100 min. The model predicts that 10% of the hemoglobin is oxidized to the ferric form after oral doses of 15.9 mg/kg in male rats and 11.0 mg/kg in female rats and after intravenous doses of 8.9 and 7.1 mg/kg in male and female rats, respectively. The t(1/2) for recovery from methemoglobinemia was 60 to 120 min depending on dose and route of administration. A sensitivity analysis of the model was performed to identify to which parameters the predictions of the model were most sensitive and guide attempts to simplify the model. Replacement of the V(max) of methemoglobin reductase with a value representative of humans predicted a 10% methemoglobinemia following an intravenous dose of 5.8 mg/kg, in close agreement with an observed value of 5.7 mg/kg for humans.

Topics: Animals; Female; Hemoglobins; Male; Methemoglobin; Methemoglobinemia; Models, Biological; Rats; Rats, Inbred F344; Sodium Nitrite

Topics: Blood Gas Analysis; Child; Humans; Male; Methemoglobinemia; Sodium Nitrite

Topics: Acetaminophen; Aged; Analgesics, Non-Narcotic; Arthritis, Rheumatoid; Diabetes Mellitus, Type 2; Drug Combinations; Female; Food Preservatives; Humans; Methemoglobin; Methemoglobinemia; Sodium Nitrite

K-Cl cotransport (COT) is the coupled movement of K and Cl, present in most cells, associated with regulatory volume decrease, susceptible to oxidation and functionally overexpressed in sickle cell anemia. The aim of this study was to characterize the effect of the oxidant nitrite (NO2-) on K-Cl COT. NO2- is a stable metabolic end product of the short-lived highly reactive free radical nitric oxide (NO), an oxidant and modulator of ion channels, and a vasodilator. In some systems, the response to NO2- is identical to that of NO. We hypothesized that NO2- activates K-Cl COT. Low potassium (LK) sheep red blood cells (SRBCs) were used as a model. The effect of various concentrations (10(-6) to 10(-1) m) of NaNO2 was studied on K efflux in hypotonic Cl and NO3 media, Cl-dependent K efflux (K-Cl COT), glutathione (GSH), and methemoglobin (MetHb) formation. In support of our hypothesis, K efflux and K-Cl COT were stimulated by increasing concentrations of NaNO2. Stimulation of K efflux was dependent upon external Cl and exhibited a lag phase, consistent with activation of K-Cl COT through a regulatory mechanism. Exposure of LK SRBCs to NaNO2 decreased GSH, an effect characteristic of a thiol-oxidizing agent, and induced MetHb formation. K-Cl COT activity was positively correlated with Methb formation. N-ethyl-maleimide (NEM), a potent activator of K-Cl COT, was used to assess the mechanism of NO2- action. The results suggest that NEM and NO2- utilize at least one common pathway for K-Cl COT activation. Since NaNO2 is also a well known vasodilator, the present findings suggest a role of K-Cl COT in vasodilation.

Topics: Animals; Carrier Proteins; Chlorides; Erythrocyte Membrane; Ethylmaleimide; Glutathione; Hypotonic Solutions; Ion Transport; K Cl- Cotransporters; Methemoglobinemia; Nitric Oxide; Osmolar Concentration; Potassium; Sheep; Sodium Nitrite; Symporters

Methemoglobin formation caused by a liniment solution containing sodium nitrite (30 g/L and 140 g/L) was studied in rats with normal or abraded skin, by measuring the methemoglobin concentration before and after application of liniment solutions with differing nitrite concentration.. Each liniment solution (120 microL) was applied. Methemoglobin was measured for 180 minutes using a hemoximeter. Simultaneously, arterial blood pressure and cutaneous blood flow was measured by laser Doppler flowmetry and a pressure transducer.. After the application of each liniment solution to normal skin, the methemoglobin concentration was not significantly modified depending on the time after application. Application of liniment solution to abraded skin (140 g/L) resulted in a marked increase in methemoglobin concentration. A remarkable decrease in arterial blood pressure and subcutaneous blood flow were observed after application of liniment solution to abraded skin (140 g/L).. Each of these findings are characteristic of nitrite and they imply the percutaneous absorption of nitrite. Regardless of the nitrite concentration, the methemoglobin concentration was consistently higher in abraded skin than in normal skin.

Topics: Administration, Cutaneous; Animals; Blood Pressure; Dermabrasion; Laser-Doppler Flowmetry; Liniments; Male; Methemoglobinemia; Rats; Rats, Wistar; Regional Blood Flow; Skin; Skin Absorption; Sodium Nitrite

Three teenagers from a butcher's household were admitted to hospital as emergency case after eating sausages. The local consultant in communicable disease control was immediately asked to help investigate the cause of their food poisoning. The cases were treated for methaemoglobinaemia. Investigations revealed that the sausage meat had been prepared using sodium nitrate (saltpetre) as a preservative at levels well in excess of those legally permitted in meat products. Prompt recognition of the cause of the food poisoning prevented the outbreak from becoming much bigger. A large quantity of the sausage meat had been prepared for commercial sale, but the butcher's children had eaten part of the batch on the evening before it was due to go on sale to the public.

Topics: Adolescent; Adult; Food Preservation; Foodborne Diseases; Humans; Male; Meat; Methemoglobinemia; Nitrates; Sodium Nitrite

A family outbreak of methaemoglobinaemia following ingestion of sausages made using 'saltpetre' is reported. Saltpetre is a generic term for several potassium and sodium based compounds. On this occasion imprecise ordering led to the use of sodium nitrite rather than the usual potassium nitrate, with extremely serious consequences.

Topics: Adolescent; Antidotes; Child; Food Handling; Food Preservatives; Humans; Male; Meat Products; Methemoglobinemia; Methylene Blue; Sodium Nitrite

We describe a case of fatal methemoglobinemia (MetHb-emia) resulting from application of liniment solution containing large quantities of sodium nitrite. As a remedial treatment of atopic dermatitis, the liniment solution was applied all over the boy's body. Autopsy findings showed no significant macroscopic or microscopic findings except blood tinted chocolate brown color and chronic atopic dermatitis over the whole surface of the body. Quantitation of the methemoglobin (MetHb) in the blood was performed using spectrophotometer; MetHb concentration of the blood was 76%. Ion chromatographic determination revealed a nitrite concentration of 1 mg/L in the serum. Such a liniment solution is not authorized by the Ministry of Public Welfare.

Topics: Administration, Topical; Child, Preschool; Dermatitis, Atopic; Fatal Outcome; Humans; Liniments; Male; Methemoglobinemia; Skin Absorption; Sodium Nitrite

The study was performed on 4 groups of male Wistar rats, receiving p.o. through 3 months every day: 1) sodium nitrite in dose 30 mg/kg b.w. x day (0.2 LD50); 2) copper chloride in dose 4.67 mg/kg b.w. x day (0.03 LD50); 3) copper chloride and sodium nitrite in amounts as above, and 4 - control group - received distilled water. The methemoglobin and hemoglobin were determined in whole blood and tryptophan in plasma 24 hours after the last intoxication. There was showed, that every day intoxication of rats with sodium nitrite cause the increase of methemoglobin concentration and decrease the free tryptophan level in the blood. There was also observed, that copper chloride, administrated together with sodium nitrite, decreases significantly his methemoglobin creating action.

Topics: Animals; Copper; Drug Administration Schedule; Male; Methemoglobinemia; Rats; Rats, Wistar; Sodium Nitrite; Tryptophan

Sodium nitrite is used commercially as a coloring agent, a food preservative and a corrosion inhibitor. Accidental poisoning usually results from the ingestion of contaminated food and water and causes gastrointestinal irritation, vasodilatation and methemoglobinemia with subsequent tissue hypoxia. We describe an unusual case of sodium nitrite-induced methemoglobinemia following the ingestion of drinking water contaminated with a corrosion inhibitor. To our knowledge this is the first report of such a case.

Topics: Adult; Female; Humans; Methemoglobinemia; Sodium Nitrite; Water Supply

To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients.. Regional poison center and regional toxicology treatment center.. Seven critically ill smoke inhalation patients referred to the regional poison center.. Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels.. The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series.. The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe.

Topics: Adult; Antidotes; Carbon Monoxide Poisoning; Carboxyhemoglobin; Combined Modality Therapy; Cyanides; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Hyperbaric Oxygenation; Infusions, Intravenous; Male; Methemoglobin; Methemoglobinemia; Middle Aged; Poison Control Centers; Poisoning; Prospective Studies; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates; Time Factors

The effects of nitrite-induced methaemoglobinaemia on adrenergic proton extrusion from rainbow trout red blood cells were studied using the pH-stat method. In control conditions adrenergic proton extrusion was completely inhibited by amiloride and was greater in deoxygenated than in oxygenated erythrocytes. Nitrite-induced methaemoglobinaemia was associated with a pronounced reduction in the catecholamine-stimulated proton efflux from both deoxygenated and oxygenated erythrocytes. In deoxygenated erythrocytes the initial proton efflux upon catecholamine stimulation decreased by 60-70%, while the percentage of methaemoglobin in the red cells increased from the control level of 1-3% to 20%. In oxygenated erythrocytes the decrease was 30% at the same methaemoglobin percentage range. It is suggested that the pronounced influence of nitrite-induced methaemoglobinaemia on adrenergic proton efflux results from an inhibition of the red cell sodium/proton exchanger by the R-like haemoglobin conformations.

Topics: Animals; Carrier Proteins; Erythrocytes; In Vitro Techniques; Ion Transport; Methemoglobinemia; Protons; Receptors, Adrenergic; Seasons; Sodium Nitrite; Sodium-Hydrogen Exchangers; Trout

Cyanide poisoning is a life threatening condition. But specific antidotes exist and can be easily prepared from available substances in hospital. Administration of antidotes will produce methemoglobin, which itself causes hypoxia. Nitrite induced methemoglobin can be extremely dangerous and even lethal. Before administering the antidotes, the diagnosis should be confirmed. Nitrite should not be given if the poisoning is mild or diagnosis is uncertain, to avoid excessive methemoglobin, dosage of sodium nitrite must be adjusted according to hemoglobin level (Table 1). Usage of sodium nitrite and sodium thiosulfate in the recommended doses are safe and effective for cyanide poisoning.

Topics: Acute Disease; Adult; Antidotes; Humans; Male; Methemoglobinemia; Poisoning; Potassium Cyanide; Sodium Nitrite; Thiosulfates

We describe two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulphate at a concentration of 15 g/l. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia.

Topics: Aged; Cathartics; Drug Contamination; Emergencies; Female; Humans; Male; Methemoglobinemia; Sodium Nitrite

Clinical efficacy of two pretreatment regimens, sodium nitrite (SN) + hydroxylamine (HA) and SN + 4-dimethylaminophenol (DMAP) were evaluated in rats by studying various biochemical variables at different time intervals. Animals given single subcutaneous (s.c.) co-administration of SN+HA or SN+DMAP showed significantly elevated levels of blood bilirubin indicating hemolytic anemia. Increased levels of blood creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT) were indicative of aseptic necrosis at the injection site. On account of low methemoglobin reductase activity in human erythrocytes, a reduced sub-clinical dose of HA or DMAP is envisaged in humans.

Topics: Aminophenols; Anemia, Hemolytic; Animals; Antidotes; Cyanides; Drug Evaluation, Preclinical; Hydroxylamine; Hydroxylamines; Male; Methemoglobinemia; Rats; Rats, Inbred Strains; Sodium Nitrite

Topics: Aminophenols; Animals; Cyanides; Disease Models, Animal; Lethal Dose 50; Male; Methemoglobin; Methemoglobinemia; Rats; Rats, Inbred Strains; Sodium Nitrite

Topics: Animals; Biochemical Phenomena; Biochemistry; Catalase; Erythrocytes; In Vitro Techniques; Malondialdehyde; Methemoglobinemia; Mice; Models, Biological; Sodium Nitrite; Superoxide Dismutase

This study was undertaken to evaluate the effects of pretreatment with calcium channel antagonists (nimodipine or verapamil) on the formation of methemoglobin produced by sodium nitrite. Unexpectedly, the pretreatment of animals with control injections of physiological saline 2 hours before the nitrite administration reduced the amount of methemoglobin found in the blood 25 minutes later. When either of the calcium channel antagonists was given 2 hours before the administration of sodium nitrite, the saline effect was eliminated. When the injections of physiological saline or either of the calcium channel blockers were divided 24 hours before the nitrite administration, all reduced the amount of methemoglobin formed relative to rats that received no pretreatment. A tentative hypothesis is that the reduction of the nitrite-induced methemoglobin can be induced by the stress of handling and intraperitoneal injection and that this stress effect can last at least 24 hours. It is likely that whatever stress-related mechanism is involved in reducing methemoglobin levels, this effect can be reduced by the presence of "L channel" voltage-sensitive calcium antagonists or their active metabolites.

Topics: Animals; Calcium Channel Blockers; Male; Methemoglobinemia; Nimodipine; Rats; Sodium Chloride; Sodium Nitrite; Verapamil

Methaemoglobinaemia may be caused by ingestion of a number of drugs, among them nitrites, some of which are remarkably toxic. This was tragically highlighted by the death of a 17 year old dental nurse after taking a single 1 g tablet of sodium nitrite. These tablets are widely used in the medical and dental profession to prevent rusting of instruments while immersed in disinfectant solutions. The toxicity of this chemical should be more widely recognized and its storage made correspondingly more secure. Methaemoglobinaemia should be considered as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause.

Topics: Adolescent; Dental Assistants; Female; Humans; Methemoglobinemia; Sodium Nitrite; Suicide

Nitrates and nitrites are widely used in the food and chemical industry. Poisoning with these agents may be potentially life-threatening as a result of the production of methaemoglobin. A group of 10 patients suffering from moderate to severe methaemoglobinaemia after accidental intoxication with a sodium nitrite salt is described. One patient died but the other 9 recovered rapidly. The low mortality rate was attributed to prompt diagnosis and institution of appropriate therapy with methylene blue and ascorbic acid.

Topics: Adult; Female; Humans; Male; Methemoglobinemia; Middle Aged; Nitrites; Sodium Nitrite

Methemoglobin formation and reduction in canine erythrocytes with inherited high Na,K-ATPase activity (HK cells) were compared with those in normal canine cells (LK cells). Nitrite-induced methemoglobin formation in hemoglobin solutions indicated that the hemoglobin from HK cells was oxidized at essentially the same rate as that of LK cells. However, methemoglobin formation in HK cells was slower due to the inhibition by high glutathione (GSH) concentration. Methemoglobin reduction was allowed to take place on nitrite-treated and washed erythrocytes in a glucose medium and was reduced more rapidly in HK cells than in LK cells. During the reduction, the amounts of lactate and pyruvate increased more rapidly in HK cells, indicating enhanced glycolysis in HK cells. It is thus evident that the hemoglobin of HK cells is more securely protected from nitrite-induced oxidation by the GSH presence in great excess and by the increase in glycolysis.

Topics: Animals; Dog Diseases; Dogs; Erythrocytes; Female; Glutathione; Hemoglobins; Methemoglobin; Methemoglobinemia; Sodium Nitrite; Sodium-Potassium-Exchanging ATPase; Time Factors

Methylene blue, at high concentrations, interferes with the estimation of methaemoglobin using the IL 282 CO-oximeter: the dye does not interfere with the method of Evelyn & Malloy for determination of methaemoglobin. In beagle bitches methylene blue causes both methaemoglobinogenesis and methaemoglobin reduction, the effect of the former being to delay the decline of methaemoglobin levels, when methylene blue is used to reverse the methaemoglobinaemia produced by sodium nitrite.

Topics: Animals; Dogs; Female; Hemoglobins; Hydrogen-Ion Concentration; Injections, Intravenous; Methemoglobin; Methemoglobinemia; Methylene Blue; Nitrites; Oxidation-Reduction; Sodium Nitrite; Spectrophotometry, Infrared

The antibacterial drug nitrofurantoin (NFT) is notorious for causing hemolytic anemia, which may be related to the methemoglobinemia, another side-effect of NFT. As NFT is photolabile, and nitrite, well known as a MetHb generator, is an important photoproduct of NFT, it seems not unlikely that light is a cause of NFT-induced MetHb formation. When rats were irradiated with UV-A immediately after oral NFT administration, the amount of MetHb significantly increased: 0.97 +/- 0.37% n = 36 (P less than 0.001 Student's t-test, control value: 0.5%). An increase in MetHb was also observed with rats simultaneously exposed to UV-A and the major photodecomposition product of NFT, viz. 5-nitrofurfural. In addition in vitro experiments proved the formation of MetHb as a result of photoactivation of NFT. Nitrite, photochemically formed from nitrofurfural and from the metabolite nitrofuroic acid, plays an important role. A dark reaction of the other photoproduct, nitrofurfural, with hemoglobin also appeared to cause a considerable amount of MetHb in vitro. However, because of rapid deactivation of nitrofurfural by either photodecomposition or metabolism, this dark reaction is not expected to contribute to the in vivo MetHb formation.

Topics: Animals; Female; Furaldehyde; Furans; Methemoglobinemia; Nitrofurantoin; Photolysis; Rats; Rats, Inbred Strains; Sodium Nitrite; Ultraviolet Rays

In three patients with severe acute cyanide poisoning, a cyanosis was observed instead of the bright pink skin coloration often mentioned as a sign in textbooks. Treatment of cardiopulmonary insufficiency is as essential as antidotal therapy and the use of sodium nitrite and 4-DMAP is not without risk as, in practice, the methemoglobin-level induced is difficult to control.

Topics: Adult; Aminophenols; Coma; Cyanides; Humans; Male; Methemoglobinemia; Methylene Blue; Nitrites; Respiration, Artificial; Sodium Nitrite; Suicide, Attempted; Thiosulfates

Studies of sodium nitrite metabolism and correlation between NaNO2 metabolism and methemoglobin formation in the blood of rats exposed to radiation have been carried out. It has been shown that, along with radiation-induced damage of OHb----MHb dynamic system, an increase in NaNO2 uptake rate by the blood is the factor causing intensification of methemoglobin formation in irradiated animals.

Topics: Animals; Male; Methemoglobinemia; Nitrites; Radiation Injuries, Experimental; Rats; Sodium Nitrite

Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1-2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, PaO2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p less than 0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis; Animals; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Hemodynamics; Lactates; Lactic Acid; Methemoglobinemia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Sodium Nitrite

The effect of amyl nitrite on the erythrocytes of adult and cord hemoglobin was examined in vitro. This study revealed that amyl nitrite caused oxyhemoglobin to become oxidized to methemoglobin wherein a rectangular hyperbolic curve was generated as the reaction progressed. This curve consisted of a reactionary log phase, and a terminal asymptotic phase only, with no inductionary lag phase. A comparative study of human cord blood oxidation times and adult blood was undertaken. It was revealed that cord blood erythrocytes were oxidized by amyl nitrite at a 5-6-fold greater rate than adult blood erythrocytes. Based on an independent Student's t-test, the time taken for cord blood erythrocytes to undergo oxidation was significantly shorter (P less than 0.05) than adult controls. This greatly enhanced reactivity of cord blood erythrocytes parallels earlier findings when sodium nitrite was used instead of amyl nitrite. However, this difference defies a simple explanation and must be attributed to many factors which may include pH, structural differences, and solubility phenomenon.

Topics: Adult; Amyl Nitrite; Anticoagulants; Edetic Acid; Erythrocytes; Fetal Blood; Heparin; Humans; Infant, Newborn; Kinetics; Methemoglobinemia; Oxyhemoglobins; Sodium Nitrite

Topics: Animals; Dimethylnitrosamine; Germ-Free Life; Kinetics; Liver; Male; Methemoglobin; Methemoglobinemia; Nitrites; Rats; Rats, Inbred Strains; Sodium Nitrite

For the purpose of ascertaining the vitamin A requirement seven experiments with 303 pigs in the live weight range between 6.5 and 114 kg were made. In three experiments under in practice conditions we checked the standard vitamin A supplement to the mixed feed with 1,732 pigs (live weight range between 8.5 and 110 kg). The supplement to vitamin-A-free rations and to those poor in or free of carotene amounted to between 0 and 8,000 IU/kg feed. Above that, between 0 and 16 mg beta-carotene and 1,000 mg nitrite/kg feed were supplemented. As long as the vitamin A store in the liver during weaning amounted to greater than 50 IU and greater than 100 IU/g at the beginning of fattening, feed intake, live weight growth and feed expenditure were not influenced by the supplement of vitamin and provitamin resp. The supplement of 250 IU resulted in the same weight growth from weaning to the end of fattening as that of 4,000 IU. Nitrite supplement had a negative effect at 250 IU, at 500 IU vitamin A consumption and weight growth tended to be only insignificantly lower. The methaemoglobin content decreasing in the course of the experiment reflects the adaptation of the pigs to the nitrite load. The consumption and growth depression caused by vitamin A deficiency could be observed from the 7th week of the experiment when casein-swelling starch rations were fed, but from the 13th week of the experiment only when cereal-soybean oilmeal rations were fed. The weight of liver, spleen, kidneys, heart and brain was not influenced by vitamin A supply. The same applies to the body composition and retention with the exception of two deficiency piglets, which contained less fat in the empty body than the control animals.

Topics: Animals; beta Carotene; Body Weight; Carotenoids; Dietary Proteins; Female; Male; Methemoglobinemia; Nutritional Requirements; Sodium Nitrite; Swine; Vitamin A

Previous reports from our laboratory indicated that prophylactic protection against cyanide intoxication in mice can be enhanced by administration of chlorpromazine when it is given with sodium thiosulfate. The mechanism of potentiation of sodium thiosulfate by chlorpromazine was studied alone and in combination with sodium nitrite. Although chlorpromazine was found to induce a hypothermic response, the mechanism of enhancement of the antagonism of cyanide by chlorpromazine does not correlate with the hypothermia produced. Various other possible mechanisms were investigated, such as rate of methemoglobin formation, enzymatic activity of rhodanese and cytochrome oxidase, and alpha-adrenergic blockade. The alpha-adrenergic blocking properties of chlorpromazine may provide a basis for its antidotal effect, since this protective effect can be reversed with an alpha-agonist, methoxamine.

Topics: Animals; Antidotes; Brain; Chlorpromazine; Cyanides; Drug Synergism; Electron Transport Complex IV; Male; Methemoglobinemia; Methoxamine; Mice; Nitrites; Potassium Cyanide; Sodium Nitrite; Thiosulfates

Topics: Aminophenols; Animals; Antibodies; Cyanides; Cytochrome-B(5) Reductase; Humans; Hydroxylamine; Hydroxylamines; Lethal Dose 50; Male; Methemoglobinemia; Mice; Nitrites; Sodium Nitrite; Species Specificity; Thiosulfate Sulfurtransferase

Two fatal cases of nitrite poisoning are described. From the identical clinical picture of both patients (fulminant fall of blood pressure, remarkable cyanosis attributed to methemoglobinemia, and "nasi" vomit), food poisoning seemed to be the most likely cause. Laboratory findings revealed that the food had been contaminated during transportation in a van by a leaking cooling fluid which contained sodium nitrite as anticorrosive agent.

Topics: Adult; Aged; Cyanosis; Female; Food Contamination; Humans; Methemoglobinemia; Nitrites; Refrigeration; Sodium Nitrite

Male mice of ICR-strain (four weeks old) were divided into seven groups, of each five animals. Sodium nitrite (NaNO2), dissolved in the physiological saline solution, was administered orally at doses of 250, 220, 110, 80, 50 and 5 mg per kg, everyday during successive seven days to each group. The forced running distance was monitored by means of the treadmill (Eiken-model) during the period of the administration and recovery. All the mice which received 250 mg/kg dose died after the single shot. The capability of muscular exercise was found decreased particularly in the groups which received 110 and 80 mg/kg of NaNO2. Mean methemoglobin level (Met-Hb) in the blood of male mice was about 1.0%. Mean Met-Hb levels were increased to about 1.2% and 3.8% after the oral administration of NaNO2 at the dose of 110 mg/kg everyday for successive 7 and 21 days, respectively. Met-Hb levels were measured by means of modified Evelyn-Malloy's method. In the groups which received 110 mg/kg or less, no significant changes in the body weight as well as the other physical functions were observed, as compared with those received only physiological saline solutions.

Topics: Animals; Male; Methemoglobinemia; Mice; Mice, Inbred ICR; Motor Activity; Nitrites; Sodium Nitrite

Topics: Adult; Air Pollutants; Air Pollutants, Occupational; Female; Food; Humans; Laboratories; Methemoglobinemia; Nitrites; Occupational Diseases; Sodium Nitrite

The effects of biotin deprivation on various plasma constituents were studied in male Sprague-Dawley rats, some of which were also treated with sodium nitrate (NaNO2), extra niacin or linoleate. A basal diet containing 15% pork fat (lard), 30% egg white and sucrose, was fed for 7 weeks, with or without a weekly supplement of 150 microgram biotin and the other substances mentioned. Biotin-deprived rats ate significantly less food, gained less weight and had lower food efficiency ratios than biotin-supplemented rats. Rats given NaNO2 in the drinking water had significantly higher levels of methemoglobin than those without it; values were highest when extra niacin or linoleate was added to the diet. Lactate was highest in deprived rats and was lowest in rats supplemented with biotin alone. Blood lipids were higher with than without biotin, regardless of NaNO2. Levels of phospholipids and triglycerides were highest when extra niacin was added to the diet. Further studies are needed to define the role of biotin in oxidation-reduction reactions and in regulation of lipid metabolism.

Topics: Animals; Biotin; Body Weight; Diet; Lactates; Linoleic Acids; Lipids; Male; Methemoglobinemia; Mice; Mice, Inbred Strains; Nicotinic Acids; Nitrites; Rats; Sodium Nitrite; Specific Pathogen-Free Organisms

Topics: Absorption; Anemia; Animals; Biological Availability; Caseins; Cattle; Dose-Response Relationship, Drug; Food Handling; Hemoglobins; Iron; Male; Meat; Methemoglobinemia; Nitrites; Rats; Sodium Nitrite

The administration of sodium nitrite (60 mg/kg, s.c.) 30 min prior to carbon tetrachloride intoxication (2 ml/kg, p.o.) significantly enhanced the rise in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and isocitrate dehydrogenase. Sodium nitrite pretreatment also enhanced the carbon tetrachloride-induced decrease in hepatic microsomal glucose-6-phosphatase activity. Microsomal diene conjugation absorption indicative of microsomal lipid peroxidation was observed following carbon tetrachloride intoxication, but was not altered by sodium nitrite pretreatment. The data indicate a potentially toxic interaction between sodium nitrite-induced methemoglobinemia and carbon tetrachloride-induced hepatic injury.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Drug Synergism; Hypoxia; Lipid Metabolism; Male; Methemoglobinemia; Nitrites; Peroxides; Rats; Sodium Nitrite; Time Factors

Topics: Animals; Cats; Cattle; Cytoplasm; Electron Spin Resonance Spectroscopy; Guinea Pigs; Hemoglobins; Horses; Lagomorpha; Methemoglobin; Methemoglobinemia; Nitrites; Nitroso Compounds; Oxidation-Reduction; Pharmacology; Poisoning; Rabbits; Rats; Research; Sodium Nitrite; Species Specificity; Swine; Toxicology

Topics: Drug Contamination; Food Additives; Humans; Methemoglobinemia; Nitrites; Sodium Nitrite

Topics: Animals; Ethane; Methemoglobinemia; Nitrites; Nitro Compounds; Nitroparaffins; Propionates; Rats; Sodium Nitrite

Topics: Ammonium Compounds; Anti-Infective Agents, Local; Burns; Humans; Methemoglobinemia; Nitrites; Quaternary Ammonium Compounds; Sodium Nitrite

Topics: Humans; Methemoglobinemia; Nitrites; Sodium Nitrite