title: Therapeutic response to single intravenous bolus administration of formate dehydrogenase in methanol-intoxicated rats.
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.
authors.affiliation: Department of Physiology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India.
authors.forename: Arumugham
authors.initials: A
authors.lastname: Muthuvel
authors.forename: Rathinam
authors.initials: R
authors.lastname: Rajamani
authors.forename: Rathinasamy
authors.initials: R
authors.lastname: Sheeladevi
mesh_terms: D000138:Acidosis / Q000188:drug therapy; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002254:Carbonates / Q000494:pharmacology; D004338:Drug Combinations; D005492:Folic Acid / Q000378:metabolism; D005560:Formate Dehydrogenases / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D006864:Hydrogenase / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D000432:Methanol / Q000506:poisoning / Q000633:toxicity*; D008727:Methotrexate / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017693:Sodium Bicarbonate / Q000494:pharmacology
chemical_list: D000931:Antidotes; D002254:Carbonates; D004338:Drug Combinations; D009097:Multienzyme Complexes; C046283:sodium bicarbonate, sodium carbonate drug combination; D017693:Sodium Bicarbonate; D005492:Folic Acid; D006864:Hydrogenase; D005560:Formate Dehydrogenases; C054017:formate hydrogenlyase; D000432:Methanol; D008727:Methotrexate