Correlation of therapeutic effect of obidoxime and dosing time in the acute intoxication by chlorfenvinphos in rats.
The ability of obidoxime with atropine and diazepam mixture to reactivate acetylcholinesterase inhibited by the organophosphorus compound chlorfenvinphos was compared in the central nervous system and peripheral tissues of rats. The animals were intoxicated with chlorfenvinphos (6 mg/kg, p.o.) and treated immediately, 24 and 48 hrs later with obidoxime (50 mg/kg, i.p.), atropine (10 mg/kg, i.p.), and diazepam (10 mg/kg, i.p.) in a single dose, or in various combinations (with 2-3 drugs) simultaneously. Total tissue acetylcholinesterase activities were monitored at 2, 72, and 168 hrs after intoxication. Enzyme activity was determined using Ellman's colorimetric method. The results of the present study show that obidoxime administered separately and jointly with atropine and diazepam 24 hrs after intoxication was effective on reactivation of chlorfenvinphos-inhibited acetylcholinesterase in the central nervous system and in the peripheral tissues. However, the application of obidoxime alone or in combination with atropine and diazepam 48 hrs after chlorfenvinphos intoxication caused an increased unfavourable effect in rats. The results obtained also indicate an unfavourable interaction of obidoxime with diazepam in the course of chlorfenvinphos poisoning, when antidotes were administered immediately, 24 and 48 hrs after intoxication.
Department of Pathophysiology, Institute of Agricultural Medicine, Lublin, Poland. grasz1@vp.lublin.pl
Grzegorz
G
Raszewski
Rafał
R
Filip
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001285:Atropine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000201:enzymology; D002709:Chlorfenvinphos / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003964:Diaphragm / Q000201:enzymology; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007366:Intercostal Muscles / Q000201:enzymology; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology; D009768:Obidoxime Chloride / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000927:Anticonvulsants; D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009768:Obidoxime Chloride; D001285:Atropine; D000110:Acetylcholinesterase; D002709:Chlorfenvinphos; D003975:Diazepam