Acute effects of acephate and methamidophos on acetylcholinesterase activity, endocrine system and amino acid concentrations in rats.
Acute effects of acephate (Ace) and methamidophos (Met) on acetylcholinesterase activity, endocrine system and amino acid concentrations were studied in rats. The rats were injected intraperitoneally with Ace (500 mg/kg) or Met (5 mg/kg) and then sacrificed at 15 or 60 min after the injection (A15 and A60 for Ace and M15 and M60 for Met). The primary aim of this study was to determine whether the mammalian toxicity of Ace is solely due to its conversion to Met or the protection of Ace against Met-inhibited AChE is also an important factor. The second aim of this study was to study the effects of Ace and Met on the endocrine system and amino acid concentrations and whether or not these effects correlate with AChE inhibition and Met accumulation. The Ace or Met injected animals did not exhibit the signs of organophosphate (OP) poisoning within 15 min after the injection, but exhibited tremors at 45 min after the injection. Blood and brain AChE activity in A15 and M15 rats exhibited 55 to 75% inhibition while the enzyme activity in A60 and M60 rats exhibited 80 to 95% inhibition. Ace was metabolized to Met in rats both in vivo and in vitro. A 5 rats had significantly higher Met concentration in their liver, brain and adrenal glands compared to M 5 rats, and A60 rats had significantly higher Met concentrations in their blood, liver, brain and adrenal glands compared to M60 rats. Thus, tissue Met concentrations in Ace-treated rats were significantly higher than in Met-treated rats and the inhibition of AChE activity was not consistent with the amount of metabolically formed Met, supporting the hypothesis that the Ace protection plays a role in the overall toxicity. Ace and Met both impaired circulating blood hormone and amino acid concentrations in rats. The endocrine effects of Ace and Met differed from their cholinergic effects, and were not proportional to the amount of Met present in different tissues obtained from the treatment groups. Plasma ACTH concentration was elevated in M60 rats but not in A60 rats. Thus, Ace may indirectly protect the pituitary against the toxic effects of Met. Unlike plasma ACTH levels, serum corticosterone and aldosterone levels were elevated in both A60 and M60 rats. Therefore, the effect of Met on the adrenal cortex may be mediated by the pituitary gland, while the effect of Ace may be due to direct Ace-gland interaction. The decrease in the levels of some of the serum amino acids showed an increase in the energy demands in the treatment groups.
Spassova
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Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA.
White
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T
Singh
A K
AK
D000110:Acetylcholinesterase / Q000378:metabolism*; D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D005260:Female; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D063088:Phosphoramides; D051381:Rats; D017208:Rats, Wistar; D014202:Tremor / Q000139:chemically induced
D000596:Amino Acids; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D063088:Phosphoramides; C001969:acephate; D000450:Aldosterone; C014655:methamidophos; D000324:Adrenocorticotropic Hormone; D000110:Acetylcholinesterase; D003345:Corticosterone