Ranitidine in Acute High‐Dose Organophosphate Exposure in Rats: Effect of the Time‐Point of Administration and Comparison with Pyridostigmine

Abstract

Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H 2 ) receptor blocker ranitidine is among H 2 blockers the most potent inhibitor of acetylcholinesterase but roughly three to four orders of magnitude less potent than paraoxon (an irreversible organophosphate esterase inhibitor) or pyridostigmine (a reversible carbamate esterase inhibitor). We have previously shown that in vitro ranitidine confers some protection against inhibition of cholinesterases by paraoxon and that in vivo it both increases the number of rats surviving an acute paraoxon exposure and also protects to some degree the cholinesterases from organophosphate inhibition. The purpose of the study was to compare in a prospective non-blinded study, in a rat model of acute high-dose paraoxon exposure, ranitidine with pyridostigmine either administered simultaneously or 30 min. before exposure. There were 36 rats in each of the 5 groups.

Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A review

“…It is therefore conceivable that the reversible AChE inhibitors given as pretreatment in our studies, by temporarily increasing ACh levels and stimulating muscarinic receptors, boost AChE production, which in turn attenuates the deleterious effects of subsequent AChE inhibition exerted by OPCs. In support of this hypothesis, we have observed that optimal protection is conferred, when AChE inhibitors are administered 30–90 minutes before OPC exposure (Petroianu, Hasan, Nurulain, Arafat, et al, ; Petroianu, Hasan, Nurulain, Shafiullah, et al, ).…”

Haemato-pathological effect of dichlorvos on blood picture and liver cells of albino rats

“…It is established that many of these pesticides can produce some adverse effects on the liver and other vital organs in the body through their mode of action or by the production of free radicals (Khan et al, 2005). Dichlorvos acts mainly by irreversibly inhibiting the enzyme acetylcholinesterase (AChE) at cholinergic junctions of the central nervous system (Petroianu et al, 2006) which induce oxidative stress and results to hepatotoxicity in rat (Gupta et al, 2005) Liver plays a crucial role in detoxification of harmful chemical substances, it is the site of biotransformation of many toxic compounds into less harmful products thereby reducing their toxicity and ensuring structural stability of the body. Haematological parameters serve as important indices in the monitoring and management of health status.…”

Prophylactic administration of non‐organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone

“…It may therefore well be that the cholinesterase inhibitors given as pre‐treatment in our study, by temporarily increasing ACh levels and stimulating muscarinic receptors, induce overproduction of the AChE protein, which thereafter protects the organism against cholinesterase inhibition exerted by OPCs. In agreement with this assumption, we have observed that optimal protection is conferred, when cholinesterase inhibitors are administered 30–90 min before OPC exposure (Petroianu et al ., , ).…”