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1.
Toxicol Lett ; 161(2): 89-95, 2006 Feb 20.
Article in English | MEDLINE | ID: mdl-16185830

ABSTRACT

Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 1.2.1.2) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be concluded that single bolus infusion of formate dehydrogenase facilitates fast removal of formate, a highly toxic metabolite in methanol poisoning.


Subject(s)
Antidotes/pharmacology , Formate Dehydrogenases/administration & dosage , Formate Dehydrogenases/pharmacology , Hydrogenase/administration & dosage , Hydrogenase/pharmacology , Methanol/toxicity , Multienzyme Complexes/administration & dosage , Multienzyme Complexes/pharmacology , Acidosis/drug therapy , Animals , Antidotes/administration & dosage , Antidotes/therapeutic use , Carbonates/pharmacology , Drug Combinations , Folic Acid/metabolism , Formate Dehydrogenases/therapeutic use , Hydrogenase/therapeutic use , Methanol/poisoning , Methotrexate/pharmacology , Multienzyme Complexes/therapeutic use , Rats , Sodium Bicarbonate/pharmacology
2.
J Environ Monit ; 5(3): 477-82, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12833992

ABSTRACT

In order to encourage more exposure measurements to be performed, a formic acid gas-phase biosensor has been developed for this purpose. In the present paper, an enzyme based biosensor has been validated with respect to analyte selectivity and on-site use. To ensure that the sampler developed measures the compound of interest the biosensor was exposed to three near structural homologues to formic acid, i.e. acetic acid, methanol and formaldehyde. These vapours were generated with and without formic acid and the only compound that was found to have an effect on the performance of the biosensor, albeit a small one, was acetic acid. The field test was performed in a factory using formic acid-containing glue for glulam products. In parallel to the measurements with the biosensor a well defined reference method was used for sampling and analysing formic acid. It was found that the biosensor worked satisfactorily in this environment when used in a stationary position. It was also shown that the biosensor could determine formic acid vapour concentrations down to 0.03 mg m(-3).


Subject(s)
Environmental Monitoring/methods , Formate Dehydrogenases/pharmacology , Formates/analysis , Biological Assay , Reference Values , Volatilization
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