Assessment of diphenhydramine effects against acute poisoning induced by the organophosphate insecticide dichlorvos in chicks

Introduction Organophosphate (OP) insecticides are commonly used in veterinary practice and public health (Coggon 2002; Jaga & Dharmani 2003; Wilson 2005). They induce poisoning in mammals and avian species by irreversible inhibition of cholinesterase (ChE) activity at the nerve terminals and neuromuscular junctions causing accumulation of acetylcholine. As a result of ChE inhibition, signs of cholinergic toxicity appear which are characterized by muscarinic, nicotinic and central nervous system effects (Osweiler 1996; Kwong 2002; Wilson 2005). The standard antidote for OP poisoning in man and animals is the muscarinic receptor antagonist atropine sulfate (Osweiler 1996; Kwong 2002; Wilson 2005). The antihistamine diphenhydramine has been reported by several studies to counteract OP-induced lethality and poisoning in laboratory animals in a manner similar to atropine (Mohammad et al 1989; Faris & Mohammad 1997; Mohammad et al 2002; Bird et al 2002; Yürümez et al 2007). Earlier reports suggested the possibility of beneficial therapeutic efficacy of diphenhydramine in dogs (Clemmons et al 1984) and man (Moody & Terp 1988) suffering from OP poisoning. Thereafter, studies originating from our laboratories have documented and characterized the antidotal and therapeutic effects of diphenhydramine against experimental OP-induced lethality and toxicoses in mice (Mohammad et al 1989; Faris & Mohammad 1996a, 1997) and rats (Mohammad et al 2002). Later on other investigators further confirmed the action of diphenhydramine against OP-induced lethality in rats (Bird et al 2002). Diphenhydramine also attenuates OP induced pancreatic (Yürümez et al 2007) and cardiac (Yavuz et al 2008) injuries in rats. The protective and antagonistic effects of diphenhydramine against OP poisoning have been attributed to Abstract. Objective: The study was designed to assess the protective and ameliorative effects of the antihistamine diphenhydramine against a model of acute organophosphate insecticide (dichlorvos) poisoning in 7-14 day-old chicks. Material and Methods: The acute (24 h) oral median lethal doses (LD50) of dichlorvos either alone or with concomitant diphenhydramine (10 mg kg -1, i.m.) or atropine (2 mg kg 1, i.m.) were determined in the chicks by the up-and-down method. The protective and ameliorative effects of diphenhydramine on the signs of dichlorvos poisoning were examined and compared with those of atropine. Plasma and whole brain cholinesterase activities of chicks treated with diphenhydramine and/or dichlorvos were measured by an electrometric method. Results: Diphenhydramine at 10 mg kg-1, intramuscularly (i.m.) immediately after oral dosing with dichlorvos increased the oral LD50 value of the insecticide from 6.49 to 17.14 mg kg-1, whereas atropine at 2 mg kg-1, i.m. increased it to 22.55 mg kg-1. The oral dosing of dichlorvos at 8 mg kg-1 caused acute signs of cholinergic poisoning in the chicks. The best effective dosage of diphenhydramine was at 10 mg kg-1, i.m. immediately after the oral dichlorvos dosing, which significantly increased the latencies to onset of signs of poisoning and significantly prevented the 2 h and 24 h lethalities. Diphenhydramine also significantly decreased the occurrence of signs of poisoning and reduced total toxicity score in the chicks. Diphenhydramine, similar to atropine, given at times of -15, 0 and + 5 min relative to the time of dichlorvos dosing also ameliorated dichlorvos-induced poisoning in the chicks to varying extents. Dichlorvos alone at the oral doses of 2 and 4 mg kg-1 significantly reduced cholinesterase activity in the plasma and whole brain. Diphenhydramine at 10 mg kg-1, i.m. immediately after oral dichlorvos dosing at 4 mg kg-1 significantly but partially ameliorated cholinesterase inhibition caused by the insecticide in the whole brain of the chicks. Conclusion: The results suggest that diphenhydramine has protective and ameliorative effects against a model of acute organophosphate poisoning in chicks.