Hemoglobin-to-methemoglobin

Nitrites may be used as an antidote for cyanide poisoning if given rapidly. They convert hemoglobin to methemoglobin, which binds cyanide in the blood before reaching the tissues. Oxygen is also given if possible. 

Finally, it should be mentioned that HA is effective as an antidote against cyanide poisoning by virtue of converting ca 20% of the hemoglobin to methemoglobin. This will be discussed at length in Section ILF. 

The hydrolysis of some amides may be catalyzed by a liver microsomal carboxyl esterase, as is the case with phenacetin (Fig. 4.44). Hydrolysis of the acetylamino group, resulting in deacetylation, is known to be important in the toxicity of a number of compounds. For example, the deacetylated metabolites of phenacetin are thought to be responsible for its toxicity, the oxidation of hemoglobin to methemoglobin. This toxic effect occasionally occurs in subjects taking therapeutic doses of the drug and who have a deficiency in the normal pathway of metabolism of phenacetin to paracetamol. Consequently, more phenacetin is metabolized by deacetylation and subsequent oxidation to toxic metabolites (chap. 5, Fig. 24). 

Nitrite, which may be administered as sodium nitrite solution or inhaled as amyl nitrite, will oxidize hemoglobin to methemoglobin. This oxidized form of hemoglobin will bind cyanide more strongly than cytochrome a-a3 and therefore tend to remove the cyanide bound inside cells and sequester it in the blood from where it is more readily eliminated. 

Nitrobenzene is a pale yellow oily liquid (mp, 5.7°C bp, 211°C) with an odor of bitter almonds or shoe polish. It is produced mainly for the manufacture of aniline. It can enter the body through all routes and has a toxicity rating of five. Its toxic action is much like that of aniline, including the conversion of hemoglobin to methemoglobin, which deprives tissue of oxygen. Cyanosis is a major symptom of nitrobenzene poisoning. 

When the taurine chloramine uptake rate exceeds the rate of NADPH-dependent regeneration of GSH, there is a net loss of cellular GSH level, causing protein-thiol oxidation, ATP loss, and disruption of cellular metabolism. Heme moieties are the other target of chloramine attack on cellular constituents. Oxidation of hemoglobin to methemoglobin (and other hemoproteins to their oxidized derivatives) occurs at 10-fold excess of chloramine taurine molar concentration compared... 

Several in vitro studies proved that treatment of intact erythrocytes with nitrites causes the oxidation of hemoglobin to methemoglobin by radical generation along with a decrease in reduced glutathione (GSH) level associated with erythrocyte membrane dysfunctions and namely altered cell ionic flux, lipid peroxidation, and perturbation of membrane transport (Batina et al 1990 May et al 2000). Nitrate/ nitrite-induced oxidation of biological molecules potentiates reactions, which interfere in the oxidative chain and which can affect some antioxidant systems. 

The cyanide antidote kit contains amyl nitrate, sodium nitrate, and sodium thiosulfate. Nitrates convert hemoglobin to methemoglobin, which in turn competes for cyanide with the mitochondrial oxidase complex. Amyl nitrate pearls, administered by inhalation, can be utilized as a first aid measure when intravenous (IV) access is impossible or will be delayed. If IV access is available, IV sodium nitrate is preferred, followed by sodium thiosulfate. Sodium thiosulfate reacts with cyanide to form nontoxic thiocyanate, which is then excreted into the urine. 

Nitric oxide oxidizes hemoglobin to methemoglobin, two-thirds of which is reduced by nicotinamide adenine dinu-cleotide (NAD) methemoglobin reductase (1). Several ethnic groups, such as native Americans, have NAD methemoglobin reductase deficiency. There have been reports of methemoglobinemia after accidental overdosage of inhaled nitric oxide in native Americans and others (1). 

Aminobiphenyl is one of a number of chemicals that cause methemoglobinemia, or conversion of hemoglobin to methemoglobin, which reduces the ability of the blood to carry oxygen to tissues. In addition, the active metabolite (see above) is believed to produce cancer through its reaction with cellular DNA. In animal studies, the observed incidence of 4-aminobiphenyl adducts with bladder epithelium DNA correlated well with the observed bladder tumor incidence. 

Nitrate and nitrites can combine with secondarys amines to form dimethylnitrosamines, which are acutely toxic and cause centrilobular necrosis, fibrous occlusion of central veins, and pleural and peritoneal hemorrhages in animals. In the body nitrates are converted to nitrites, which can oxidize hemoglobin to methemoglobin and lead to cyanosis. 

Nitrites bind to hemoglobin causing oxidation of hemoglobin to methemoglobin, which is unable to transport oxygen. When methemoglobinemia exceeds 10-15%, cyanosis may become apparent. 

B. Treatment with nitrites to convert hemoglobin to methemoglobin. 

Nitrite ion has been shown to be toxic in the human body and animals, since diazotization of amines present in the body can lead to carcinogenic N-nitroso compounds. Furthermore, nitrite oxidizes hemoglobin to methemoglobin which is incapable of binding oxygen. In contrast, nitrate itself is not toxic but is easily reduced to nitrite by microorganisms. 

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