The antidotes atropine and pralidoxime distinctively recover cardiorespiratory components impaired by acute poisoning with chlorpyrifos in rats

Igor Simões Assunção Felippe, Cláudia Janaína Torres Müller, Alciene Almeida Siqueira, Leonardo dos Santos, Alana Cavadino, Julian Francis Richmond Paton, Vanessa Beijamini, Karla Nívea Sampaio*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

Abstract

In a previous work we showed that the organophosphate pesticide (OP) chlorpyrifos (CPF) reduces the protective chemoreflex and baroreflex responses in rats. However, whether the antidotes atropine (ATR) and pralidoxime (2-PAM) are capable of restoring these reflex functions remains unexplored. Rats were poisoned with CPF (30 mg.kg−1, i.p.) and one hour after the intoxication, ATR (10 mg.kg−1, i.p.) and 2-PAM (40 mg.kg−1, i.p.) were administrated separately or in combination. Cardiorespiratory parameters were recorded in awake rats 24 h after CPF. Systolic blood pressure (SBP) and heart rate (HR) variability and spontaneous baroreflex sensitivity (sBRS) were derived from undisturbed recordings (30 min), while chemoreflex was assessed through potassium cyanide (KCN) i.v. injections (10, 20, 40, 80 μg/rat). CPF poisoning increased SBP variability and low frequency/high frequency (LF/HF) ratio of the HR variability spectrum, indicating autonomic imbalance with increased cardiac sympathetic tone. sBRS was not changed. Treatment with 2-PAM restored SBP variability, whilst both antidotes increased LF/HF ratio. CPF poisoning reduced the hypertensive, bradycardic and tachypneic chemoreflex responses. Chemoreflex-induced hypertensive response was restored by 2-PAM treatment, while ATR recovered the bradycardic response. Both antidotes restored the chemoreflex tachypneic response. Our data show distinct effects of ATR and 2-PAM on cardiorespiratory parameters affected by OP poisoning. While 2-PAM rescued the chemoreflex hypertensive response, ATR reversed chemoreflex bradycardic dysfunction. Although 2-PAM clinical use is questioned in some countries, our data indicate that summation of effects of both antidotes appears beneficial on the cardiorespiratory system and peripheral chemoreflex function.

Original languageEnglish
Article number114879
Number of pages11
JournalToxicology and Applied Pharmacology
Volume389
Early online date10 Jan 2020
DOIs
Publication statusPublished - 15 Jan 2020

Keywords

  • Atropine
  • Cardiorespiratory
  • Chlorpyrifos
  • Organophosphate
  • Pralidoxime

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    Felippe, I. S. A., Müller, C. J. T., Siqueira, A. A., dos Santos, L., Cavadino, A., Paton, J. F. R., Beijamini, V., & Sampaio, K. N. (2020). The antidotes atropine and pralidoxime distinctively recover cardiorespiratory components impaired by acute poisoning with chlorpyrifos in rats. Toxicology and Applied Pharmacology, 389, [114879]. https://doi.org/10.1016/j.taap.2020.114879