Recognition and Assessment of Antidotal Effects of Diphenhydramine against Acute Carbaryl Insecticide Poisoning in a Chick Model

Abstract

Diphenhydramine antagonizes poisoning produced by cholinesterase (ChE) inhibiting insecticides. This study examines the effects of diphenhydramine against acute poisoning induced by the carbamate insecticide carbaryl in a chick model. The effects of diphenhydramine on the 24 h median Lethal Dose (LD50), and acute toxicity of carbaryl were assessed in chicks (7-15 days old). The plasma and whole brain ChE activities were measured electrometrically in vitro and in vivo. Diphenhydramine at 10mg/Kg Body wt. administered intramuscularly 15 min before carbaryl dosing increased the oral LD50 value of carbaryl (207 mg/Kg Body wt.) by 62%. Carbaryl at 250 mg/Kg Body wt. has orally produced toxidrome of cholinergic poisoning with 100% lethality in 24 h. Diphenhydramine (10mg/ Kg Body wt.) used 15 min before carbaryl (250mg/Kg Body wt., orally) was the most effective dose (vs 5 and 20mg/Kg Body wt.) in delaying carbaryl-toxicity and increasing survivals in chicks. The intramuscular median effective dose (ED50) of diphenhydramine which prevented 24 h carbaryl-death in chicks was 8.6mg/ Kg Body wt. The antidotal response to diphenhydramine was similar to that of the standard antidote atropine sulfate. Diphenhydramine at 10mg/Kg Body wt., given immediately after carbaryl (200mg/Kg Body wt.), reduced the percentages of plasma and whole brain ChE inhibitions in vivo by 12- and 13%, respectively. Carbaryl (10μmol/L) in vitro inhibited ChE activities in the plasma and brain by 53 and 77%, respectively; these inhibitions were reduced by 13- and 14%, respectively, when diphenhydramine (10μmol/L) was added to in vitro reactions. Diphenhydramine exerted antidotal action against a model of acute and lethal carbaryl intoxication in chicks.