Cardiorespiratory Effects Following Acute Exposure to Pyridostigmine Bromide and/or N,N-Diethyl-m-toluamide (DEET) in Rats

Abstract

The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyridostigmine bromide (PB), and the insect repellent N, N-diethyl-m-toluamide (DEET) are combined was first described during studies of chemical mixtures that were targeted as potential causative agents of Gulf War illnesses. This study was intended to provide insight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in conscious freely moving rats using whole-body plethysmography. Cardiovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respiration and increased blood pressure. Arterial pH levels were decreased, whereas pO(2) and pCO(2) remained at control levels. Administration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were unaltered. A higher dose of DEET (500 mg/kg) also decreased respiratory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and elevated pCO(2). Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual effects of PB or DEET, and significantly increased survival after coexposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.

Phospholipid profiling of plasma from GW veterans and rodent models to identify potential biomarkers of Gulf War Illness

“…Therefore, we used 200 mg/kg of PER in order mimic a high-level exposure, which has shown adverse pathological outcome in previous studies [34,41,47,50–53]. The doses of PB and PER are less than one fifth and one half of the known LD50 values in rodents, respectively [54,55]. Six months post exposure, mice were euthanized, and plasma was collected.…”

In-vitro permeation of the Insect repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone

“…The extent of transdermal absorption from topical application was reported to be 11±51% (Smith et al 1963;Feldmann & Maibach 1970;Spencer et al 1979). Systemic absorption in humans is responsible for the known adverse effects of DEET, including cutaneous or allergic reactions, hypotension, headaches, disorientation and encephalopathy (Miller 1982;Baynes et al 1997;Fradin 1998;Chaney et al 2002). Because there is no effective human vaccine currently available against the West Nile virus and most other repellents are either short-lasting or ineffective, Health Canada started the recommendation in summer 2003 that DEET could be used in infants as young as 6 months old (Koren et al 2003).…”

Cholinergic stimulation with pyridostigmine protects myocardial infarcted rats against ischemic-induced arrhythmias and preserves connexin43 protein

“…Several studies have shown that PYR elicited bradycardia in healthy subjects (10,14,42) and infarcted patients (5,9). However, to our knowledge, few studies have evaluated the hemodynamic effects of acute PYR administration, e.g., over several hours or up to 1 wk (12,53). No changes in HR or AP (12,53) were observed in response to PYR.…”

“…However, to our knowledge, few studies have evaluated the hemodynamic effects of acute PYR administration, e.g., over several hours or up to 1 wk (12,53). No changes in HR or AP (12,53) were observed in response to PYR. These differences may be due to different methodological approaches, such as the means of administration and/or doses.…”