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Regulatory toxicology and pharmacology : RTP2007; 50(2); 200-205; doi: 10.1016/j.yrtph.2007.11.006

Selective inhibition of butyrylcholinesterase in vivo in horses by the feed-through larvacide Equitrol.

Abstract: The organophosphate insecticide tetrachlorvinphos (TCVP, Rabon) is the active ingredient in "feed-through" larvacides (e.g., Equitrol) for fly control around horse stables. As with other organophosphates, TCVP elicits toxicity by inhibiting acetylcholinesterase, leading to accumulation of the neurotransmitter acetylcholine and cholinergic signs. Relatively little is known, however, on the effects of TCVP-containing larvacides on acetylcholinesterase or other esterases in horses. Previous in vitro studies indicated that horse plasma cholinesterase activity was substantially (>10,000-fold) more sensitive than erythrocyte cholinesterase activity to inhibition by TCVP. In the current study, we examined the relative proportion of acetylcholinesterase and butyrylcholinesterase activities in horse plasma and muscle, and evaluated the in vivo effects of Equitrol on target and non-target esterases following oral feeding in horses. In vitro inhibition studies suggested that essentially all cholinesterase activity in horse plasma was butyrylcholinesterase, while muscle contained >90% acetylcholinesterase activity. For in vivo studies, adult, male horses (364-590kg; n=3/treatment group) were given either sweet feed alone or sweet feed supplemented with Equitrol daily for 21 consecutive days at the recommended rate. Clinical signs (vital signs, abdominal auscultation, ophthalmic exam, body temperature) were recorded on a daily basis. Heparinized blood samples were taken at days -1, 1, 3, 7, 21, 28, and 42 while muscle (semimembranosus) biopsies were taken under aseptic conditions on days -1 and 21. No signs of overt toxicity were noted at any time during the study. Plasma cholinesterase activity was significantly inhibited (33%) in larvacide-treated horses as early as one day after treatment and peak inhibition (69-71%) was noted at days 7 and 21. Following cessation of dosing, plasma cholinesterase activity recovered (46% and 83% of control on days 28 and 42, respectively). Neither erythrocyte cholinesterase activity nor plasma carboxylesterase activity was affected by larvacide treatment in vivo. Muscle cholinesterase activity was highly variable among individual horses (pre-treatment range: 0.50-4.92nmole/min/mg protein), but there was no suggestion of a treatment-related reduction in muscle cholinesterase activity. These in vivo results confirm our previous in vitro studies indicating marked differential sensitivity of horse plasma and erythrocyte cholinesterase to inhibition by TCVP. Furthermore, the results suggest that recommended dosing levels of the TCVP-containing larvacide in horses are unlikely to affect acetylcholinesterase activities or disrupt cholinergic neurotransmission in target tissues.
Publication Date: 2007-11-28 PubMed ID: 18166255DOI: 10.1016/j.yrtph.2007.11.006Google Scholar: Lookup
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Summary

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This research studied the effects of an organophosphate insecticide, tetrachlorvinphos (TCVP), on the cholinesterase activities in horses. It found that the TCVP-containing larvicide Equitrol predominantly inhibited butyrylcholinesterase activity in horse plasma, with no notable impact on acetylcholinesterase activity in the muscle or erythrocyte cholinesterase, thus posing minimal risk to normal cholinergic neurotransmission in horses.

Investigation of the Impact of Tetrachlorvinphos on Horses

  • The active ingredient in larvacides like Equitrol is an organophosphate insecticide known as tetrachlorvinphos (TCVP). These larvacides are used in controlling flies in environments raising horses.
  • The researchers were interested in studying whether thus insecticide affected the enzyme acetylcholinesterase in horses, as it is known to cause toxicity by inhibiting this enzyme, leading to an accumulation of the neurotransmitter acetylcholine, which can cause signs of cholinergic toxicity.
  • Before this study, little was known about how TCVP affected acetylcholinesterase or other cholinesterase enzymes in horses.

Components of the Study

  • The study was carried out both in vitro (outside a living organism) and in vivo (within a living organism). The in vitro studies showed that all cholinesterase activity in horse plasma was butyrylcholinesterase, while muscle contained over 90% acetylcholinesterase activity.
  • In the in vivo section of the study, adult male horses were given feed supplemented with Equitrol daily for three weeks and their health was closely monitored. Blood samples were taken regularly, and muscle biopsies were also done before and after the study period.
  • Noticeably, no signs of overt toxicity were noted at any time during the study from the ingestion of the TCVP-containing larvicide.

Findings of the Study

  • Results showed that plasma cholinesterase activity was significantly inhibited in larvicide-treated horses one day after treatment started, with peak inhibition observed at around one week and three weeks into the study. However, cholinesterase activity gradually improved after cessation of the treatment.
  • Noteworthy was that neither erythrocyte cholinesterase activity nor plasma carboxylesterase activity was affected by the larvicide treatment during the study. Also, there was no suggestion of a treatment-related reduction in muscle cholinesterase activity.
  • The in vivo findings from this study acted as a confirmation for the previous in vitro studies, which indicated a marked difference in the sensitivity of horse plasma and erythrocytes cholinesterase to inhibition by TCVP.
  • The research concluded that recommended dosing levels of the TCVP-containing larvicide in horses are unlikely to affect acetylcholinesterase activities or disrupt cholinergic neurotransmission in target tissues.

Cite This Article

APA
Karanth S, Holbrook T, MacAllister C, Pope CN. (2007). Selective inhibition of butyrylcholinesterase in vivo in horses by the feed-through larvacide Equitrol. Regul Toxicol Pharmacol, 50(2), 200-205. https://doi.org/10.1016/j.yrtph.2007.11.006

Publication

ISSN: 0273-2300
NlmUniqueID: 8214983
Country: Netherlands
Language: English
Volume: 50
Issue: 2
Pages: 200-205

Researcher Affiliations

Karanth, Subramanya
  • Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078, USA.
Holbrook, Todd
    MacAllister, Charles
      Pope, Carey N

        MeSH Terms

        • Animals
        • Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / toxicity
        • Butyrylcholinesterase / blood
        • Cholinesterase Inhibitors / toxicity
        • Data Interpretation, Statistical
        • Drug Combinations
        • Erythrocytes / drug effects
        • Erythrocytes / enzymology
        • Esterases / blood
        • Horses / physiology
        • Insecticides / toxicity
        • Male
        • Muscle, Skeletal / drug effects
        • Muscle, Skeletal / enzymology
        • Tetraisopropylpyrophosphamide / toxicity

        Citations

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