Methemoglobin production

Goldstein RS, Rickert DE. 1984. Relationship between red blood cell uptake and methemoglobin production by nitrobenzene and dinitrobenzene in vitro. Life Sci [I] 36 121-126. 

If death does not occur from exposure, the cyanide ion is metabolized to thiocyanate and the ion is excreted in urine. The process on conversion to thiocyanate involves the enz)mie rhodanese in the presence of thiosulfate (Hartung 1991). This process also brought about another procedure and is used in conjunction with methemoglobin production therapy to counteract cyanide poisoning. 

Poison Treatment As discussed previously, methemoglobin binds well and competes with cytochrome oxidase for cyanide ions. Consequently, the antidote developed for cyanide poisoning involves increasing the formation of methemoglobin in the blood, by inhalation of amyl nitrate vapor (Chen 1952). Antidote kits contain amyl nitrate ampoules. To administer the antidote, the ampoule is broken in a cloth such as a handkerchief and held close to the victim s nose while artificial respiration is being conducted. Resuscitation by mouth is not recommended a mechanical resuscitator should be used instead. If the victim does not respond to the amyl nitrate treatment, a medical professional would then increase the methemoglobin production by intravenous injection of sodium nitrate followed by administration of thiosulfate to increase the activity of the rhodanese enzyme. 

Figure 7. Mechanism for methemoglobin production during the redox cycling of arylhydroxylamine (ArNHOH) and nitrosoarene (ArNO) compounds. A, oxyhemoglobin B, arylhydronitroxide radical C, methemoglobin.

Exposure. Exposure to 1,3-DNB is currently measured indirectly by determining levels of methemoglobin in the blood (Donovan 1990). However, increased methemoglobin formation is not a specific response to 1,3-DNB exposure and may occur after exposure to other nitrobenzene compounds such as the other two isomers of dinitrobenzene. Determination of methemoglobin levels is widely used and is a reliable detection method. Very few methods are available for direct evaluation of 1,3-DNB levels, and they are not extensively used, probably because of the relatively rapid rate of conversion of 1,3-DNB to its degradation products (Cossum and Rickert 1985). Preliminary data suggested that the formation of adducts of 1,3,5-TNB with tissue DNA and/or with blood proteins may be useful as markers for exposure to 1,3,5-TNB (Reddy et al. 1991). Further research with both 1,3-DNB and 1,3,5-TNB in the area of adduct formation could provide valuable additional information. 

Peak methemoglobin levels may occur some hours after exposure, and it has been postulated that metabolic transformation of aniline to phenylhydroxylamine is necessary for the production of methemoglobin. Liquid aniline is mildly irritating to the eyes and may cause corneal damage. ... 

Although details are not available, extremely high exposure levels are said to cause central nervous system effects, liver damage, and chemical cyanosis ftom the production of methemoglobin. On the skin TDA produces... 

As a reducing agent, methyl hydrazine causes characteristic oxidative damage to human erythrocytes in vitro. Effects include formation of Heinz bodies and production of methemoglobin. ... 

The spontaneous reaction of nitric oxide with thiols is slow at physiological pH and the final product under anaerobic conditions is not a nitrosothiol (Pryor et al., 1982). The reaction is slow because it involves the conjugate base of the thiol (R—S"). At pH 7.0, the oxidation of cysteine by nitric oxide required 6 hr to reach completion and yields RSSR and N 2O as the products. The synthetic preparation of nitrosothiols usually involves the addition of nitrosonium ion from acidified nitrite to the thiol, or oxidation of the thiol with nitrogen dioxide under anaerobic conditions in organic solvents. Nitric oxide will form nitrosothiols by reaction with ferric heme groups, such as found in metmyoglobin or methemoglobin (Wade and Castro, 1990). It is also possible that nitrosyldioxyl radical also reacts with thiols to form a nitrosothiol. 

When the PLP reaction was explored in the absence of Tris buffer, it was found that reduction of the product with cyanogen borohydride produces a lower concentration of methemoglobin than does sodium borohydride but that both reagents yield a heterogeneous mixture of components (70). Heterogeneity of products also have been found (71,72) and it was reported that the P5Q decreased on storage if the temperature is above 4°C. Some of the... 

Chlorates Compounds formed from chloric acid(HC103), by combination of the monovalent radical -C103 a metal, hydrogen or other radical, are called chlorates. The chlorate salts are crystalline some are deliquescent they are decompd by heat with evolution of oxygen sol ih water and are powerful oxidg agents. The principal toxic effects are the production of methemoglobin in the blood destruction of red blood corpuscles... 

Qf -93.5kcal/mol Heat Capacity 23.96 cal/deg/mol at 298°K sol in w, alkalies or aq KC1 si sol in glycerol or ethyleneglycol nearly insol in abs ale or abs acet. Potassium chlorate is si to moderately poisonous the principal toxic effects are the production of methemoglobin and the destruction of red blood corpuscles. The probable lethal dose is 50-500mg/kg or betw one teaspoonful and one ounce for a 150-lb man... 

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