Protective action of M- and N-cholinoceptor blockers in acute ammonium intoxication

Abstract

Atropine and d-tubocurarine are shown to prevent convulsions in rats and mice poisoned by ammonium acetate and to protect these animals from its toxic effects. Ammonium and lactate levels in their brain were found to correlate directly with ammonium toxicity.Key Words: atropine; d-tubocurarine; ammonium intoxication; cholinoceptors; brain Hyperammonemia accompanies many human and animal diseases including hepatoencephalopathy, cirrhosis, acute liver failure, and congenital deficiency of uric cycle enzymes, to mention only a few. When blood levels of ammonium ions increase 5-10 times or more, severe central nervous system disorders, convulsions, and coma develop and death rapidly ensues [8]. The molecular basis underlying the pathogenesis of hyperammonemia-associated diseases remains, however, unknown.Toxic doses of ammonium salts induce convulsions in rats and alter acetylcholine levels in their brain [14]. Administration of ammonium chloride or acetate to animals leads to a significant fall of acetylcholinesterase activity in the brain in vivo, while high concentrations of ammonium salts reduce this activity in brain homogenates in vitro. Acetylcholinesterase inhibitors (e.g., sulfonyl halides and carbamates) are neurotoxins and cause central nervous system disorders similar to those seen after high doses of ammonium salts [13]. In view of the fact that acetylcholinesterase is an integral component of the cholinergic system, the present study aimed at clarifying the role of acetylcholine receptors in Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Laboratory of Biophysical Instrumentation, Institute of Cell Biophysics, Russian Academy of Sciences; Laboratory of Bioenergetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Mosco ammonium toxicity. To this end, the influence of specific M-and N-cholinoceptor blockers on the survival of animals acutely poisoned with ammonium acetate was examined, as was the influence of the blockers on ammonium and lactate levels in their brain, since the brain content of these metabolites has been shown to be greatly increased in acute ammonium intoxication [9]. MATERIALS AND METHODSMale Wistar rats (body weight 200-240 g) and male Swiss mice (body weight 16-20 g) were used. Acute ammonium poisoning was produced by administering ammonium acetate intraperitoneally at 7 mmol/ kg (LDs0) to rats and at 7 or 12 mmol/kg to mice. To evaluate the role acetylcholine receptors may play in the mechanism of ammonium acetate toxicity, test animals received, 15 rain prior to ammonium acetate, an intraperitoneal injection of a) the muscarine cholinoceptor blocker atropine (rats at 0.045-1.35 mg/kg, mice at 0.065-1.35 mg/kg); b) and/or the nicotine cholinoceptor antagonist d-tubocurarine (d-TC) (rats at 0.1 mg/kg, mice at 0.11 mg/kg); or c) benzohexonium (both rats and mice at 2.5 mg/kg), which is a nonspecific blocker of cholinergic receptors on autonomic ganglia. These doses of cholinergic receptor blockers were chosen because they do not affe...

Glycopyrrolate in toxic exposure to ammonia gas

“…Inhaled beta-2 agonists (salbutamol) in our patient helped in reversing the bronchospasm. Kosenko et al ,[ 5 ] have reported the protective effects of atropine in patients with acute ammonia poisoning but there have been no reports of glycopyrrolate being used in this context We preferred glycopyrrolate over atropine due to its prolonged effect on salivary and mucosal secretions with reduced cardiac side effects. [ 6 ]…”