Methemoglobin, nitrites producing

The primary function of the mammalian red blood cell is to maintain aerobic metabolism while the iron atom of the heme molecule is in the ferrous (Fe+2) oxidation state however, copper is necessary for this process to occur (USEPA 1980). Excess copper within the cell oxidizes the ferrous iron to the ferric (Fe+3) state. This molecule, known as methemoglobin, is unable to bind oxygen or carbon dioxide and is not dissociable (Langlois and Calabrese 1992). Simultaneous exposure of sheep to mixtures of cupric acetate, sodium chlorite, and sodium nitrite produced a dose-dependent increase in methemoglobin formation (Calabrese et al. 1992 Langlois and Calabrese 1992). 

Nitrates and nitrites are spread within environmental, food, industrial, and physiological systems. Nitrate may be reduced by bacteria to nitrite, and nitrite produces carcinogenic nitrosamines. Nitrite is also commonly employed in cured meat products to provide antimicrobial action, color fixation, and preservation. Nitrite can oxidize hemoglobin iron(II) to iron(III) resulting in methemoglobin, leading to a condition known as methemoglobinemia in children mainly. In excess, nitrates and nitrites may be toxic. 

Fig. 2. Absorption spectra of compounds formed upon addition of nitrite to oxyhemoglobin (Watts and Faulkner, 1953). Ferricyanide and the lower concentration of nitrite produce the typical absorption spectrum of methemoglobin. The curve obtained with the higher concentration of nitrite probably represents a mixture of...

The purpose of sodium nitrite (or amyl nitrite in the absence of IV access) is to produce methemoglobin, which binds cyanide with greater affinity than mitochondrial cytochromes. In the presence of decreased oxygen carrying capacity, as in combined exposures to cyanide and carbon monoxide (e.g., some fires), sodium nitrite can be detrimental and should be avoided. 

Electron transfer. Charged species such as nitrite ions can oxidize the iron in hemoglobin. This is a potentially toxic effect as the methemoglobin produced will not carry oxygen. 

Several nonmetallic inorganic species may act as toxicants that affect ecosystems. Spills of salts of cyanide ion, CN, from mining operations have temporarily sterilized small streams. Nitrate ion, NO3, in contaminated well water may be reduced to nitrite ion, N02, in the stomachs of ruminant animals and infants. The nitrite converts the iron(II) in blood hemoglobin to iron(III), thus producing methemoglobin, which is useless for transporting oxygen in blood. In extreme cases, fatalities have resulted in livestock and human infants. Excessive levels of carbon dioxide, C02, in water or air can be detrimental or even fatal. 

Significant levels of methemoglobinemia were produced when mice were exposed to butyl nitrites via inhalation. Pretreatment of the mice with methylene blue prevented the methemoglobin formation associated with the butyl nitrite exposure. A single intravenous dose of 30 mg kg of sodium nitrite caused methemoglobinemia in dogs. The minimum lethal dose of sodium nitrite is estimated to be 150-170 mg kg in cattle and 70-75 mg kg in pigs. 

Forage sorghum can accumulate levels of nitrates that can also produce poisoning. The nitrite ion readily reacts with hemoglobin in red blood cells, oxidizing it to methemoglobin which cannot transport oxygen. 

A condition described as "hereditary methemoglobinemia" may result from a genetic defect (Goldstein et al. 1969). The enzyme methemoglobin reductase is absent and persons are hypersensitive to any substances such as nitrite or aniline derivatives capable of producing methemoglobinemia. The trait is inherited as an autosomal recessive allele. Thus either sex may exhibit the trait which is ordinarily detected by the presence of cyanosis at birth. Such individuals would be extremely sensitive to the effects of nitrobenzene. 

---