Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole

Introduction. Ethylene glycol (EG) is relatively nontoxic but undergoes a multi-step oxidation to toxic metabolites, aldehydes and acids. The accumulation of organic acids, mainly glycolates, leads to the development of profound, life-threatening metabolic acidosis. A key therapy is an antidotal tre...

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Main Authors: Jędrzej Przystanowicz, Barbara Zielińska-Psuja, Joanna Kowalówka-Zawieja, Karina Sommerfeld
Format: Article
Language:English
Published: Poznan University of Medical Sciences 2014-03-01
Series:Journal of Medical Science
Subjects:
Online Access:https://jms.ump.edu.pl/index.php/JMS/article/view/40
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author Jędrzej Przystanowicz
Barbara Zielińska-Psuja
Joanna Kowalówka-Zawieja
Karina Sommerfeld
author_facet Jędrzej Przystanowicz
Barbara Zielińska-Psuja
Joanna Kowalówka-Zawieja
Karina Sommerfeld
author_sort Jędrzej Przystanowicz
collection DOAJ
description Introduction. Ethylene glycol (EG) is relatively nontoxic but undergoes a multi-step oxidation to toxic metabolites, aldehydes and acids. The accumulation of organic acids, mainly glycolates, leads to the development of profound, life-threatening metabolic acidosis. A key therapy is an antidotal treatment with fomepizole (4-MP), the inhibitor of the first step of EG biotransformation enzyme, alcohol dehydrogenase. Aim. The aim of the study was to demonstrate the efficacy of fomepizole in the prevention of acid-base balance disorders in acute ethylene glycol poisonings in rats. Material and methods. Adult male Wistar rats were given EG (p.o.) with single (i.p.) or multiple (p.o.) doses of 4-MP (EG 3830 and 5745 mg/kg, respectively, 4-MP in single dose of 10 mg/kg or 15 mg/kg followed by 10 mg/kg every 12 hours). Blood gas analysis was performed and blood pH, bicarbonate concentration and base excess were evaluated. Results and conclusions. The single dose of 4-MP was effective in preventing a decrease in blood pH, bicarbonate concentration and base excess during the entire experimental period (pH 7.35 vs 7.21 at hour 12, bicarbonate concentration 27.2 vs 18.3 mmol/dm3 at hour 8, base excess 1.8 vs -8.2 mmol/dm3 at hour 18). The multiple administration of 4-MP started 2 hours after EG poisoning resulted in rapid restoration of proper values of acid- -base balance parameters. Fomepizole is highly efficacious in restraining the acid-base balance disorders which are concomitant with acute ethylene glycol poisonings.
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spelling doaj.art-feb6078faad44be598a46826c67edabd2022-12-21T21:46:02ZengPoznan University of Medical SciencesJournal of Medical Science2353-97982353-98012014-03-0183110.20883/medical.e40Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizoleJędrzej Przystanowicz0Barbara Zielińska-Psuja1Joanna Kowalówka-Zawieja2Karina Sommerfeld3Department of Toxicology, Poznan University of Medical Sciences, PolandDepartment of Toxicology, Poznan University of Medical Sciences, PolandDepartment of Toxicology, Poznan University of Medical Sciences, PolandDepartment of Toxicology, Poznan University of Medical Sciences, PolandIntroduction. Ethylene glycol (EG) is relatively nontoxic but undergoes a multi-step oxidation to toxic metabolites, aldehydes and acids. The accumulation of organic acids, mainly glycolates, leads to the development of profound, life-threatening metabolic acidosis. A key therapy is an antidotal treatment with fomepizole (4-MP), the inhibitor of the first step of EG biotransformation enzyme, alcohol dehydrogenase. Aim. The aim of the study was to demonstrate the efficacy of fomepizole in the prevention of acid-base balance disorders in acute ethylene glycol poisonings in rats. Material and methods. Adult male Wistar rats were given EG (p.o.) with single (i.p.) or multiple (p.o.) doses of 4-MP (EG 3830 and 5745 mg/kg, respectively, 4-MP in single dose of 10 mg/kg or 15 mg/kg followed by 10 mg/kg every 12 hours). Blood gas analysis was performed and blood pH, bicarbonate concentration and base excess were evaluated. Results and conclusions. The single dose of 4-MP was effective in preventing a decrease in blood pH, bicarbonate concentration and base excess during the entire experimental period (pH 7.35 vs 7.21 at hour 12, bicarbonate concentration 27.2 vs 18.3 mmol/dm3 at hour 8, base excess 1.8 vs -8.2 mmol/dm3 at hour 18). The multiple administration of 4-MP started 2 hours after EG poisoning resulted in rapid restoration of proper values of acid- -base balance parameters. Fomepizole is highly efficacious in restraining the acid-base balance disorders which are concomitant with acute ethylene glycol poisonings.https://jms.ump.edu.pl/index.php/JMS/article/view/40ethylene glycolfomepizoleacid-base balanceacute poisoningrats
spellingShingle Jędrzej Przystanowicz
Barbara Zielińska-Psuja
Joanna Kowalówka-Zawieja
Karina Sommerfeld
Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
Journal of Medical Science
ethylene glycol
fomepizole
acid-base balance
acute poisoning
rats
title Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
title_full Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
title_fullStr Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
title_full_unstemmed Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
title_short Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole
title_sort acid base balance in acute ethylene glycol poisoning in rats treated with fomepizole
topic ethylene glycol
fomepizole
acid-base balance
acute poisoning
rats
url https://jms.ump.edu.pl/index.php/JMS/article/view/40
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AT barbarazielinskapsuja acidbasebalanceinacuteethyleneglycolpoisoninginratstreatedwithfomepizole
AT joannakowalowkazawieja acidbasebalanceinacuteethyleneglycolpoisoninginratstreatedwithfomepizole
AT karinasommerfeld acidbasebalanceinacuteethyleneglycolpoisoninginratstreatedwithfomepizole