The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD 50 (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.
The aim of the present work was to examine potential beneficial role of sodium bicarbonate (3 mmol/kg ip) on protective potency of trimedoxime (10 mg/kg im), obidoxime (10 mg/kg im) and atropine (10 mg/kg im) in rats poisoned with dichlorvos. Special attention was paid to the influence of co-administration of sodium bicarbonate on acid-base status in experimental animals poisoned with dichlorvos (1.3 LD 50 sc). Coadministration of sodium bicarbonate significantly increased protective effect of standard antidotes in rats poisoned with dichlorvos. Sodium bicarbonate given along with atropine/oxime produced an increase in blood pH value and correction of acidosis. In conclusion, correlation between protective effect and biochemical outcome was evident when sodium bicarbonate was added to antidotes.
Prolonged administration of sublethal doses of organophosphorus cholinesterase inhibitors results in adaptation to their toxicity. In order to investigate this phenomenon, we exposed rats to 0.2, 0.3 or 0.4 LD 50 of tabun sc daily during four weeks. AChE activities in erythrocytes, diaphragm and brain were inhibited dose-dependently after days 7 and 14 of the study and started to recover thereafter, except after 0.4 LD 50 . Tabun 0.3 LD 50 decreased body weight gain, food and water consumption during the first two weeks of the study. Spontaneous locomotor activity was significantly increased in the same interval and decreased thereafter. These findings support the assumption that both the biochemical and receptor mechanisms are responsible for the occurrence of tolerance to tabun in rats.
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