Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats

<div><p>The widely used organophosphorus pesticide chlorpyrifos (CPF) is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm’s amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.</p></div

Effects of age and CPF exposure on the sleep apnea index in juvenile (PND21) and adult (PND60) rats.

<p>A) A representative plethysmographic signal corresponding to an episode of apnea in the rat lasting longer than 2.5 sec. B) Mean numbers of apnea episodes per hour in juvenile rats (PND21 grey bars) and adult rats (PND60, black bars) in the control, CPF-1 and CPF-5 groups. **: p<0.01. The age difference between PND21 and PND60 is shown: <b>§</b>: p<0.05, $: p<0.1 PND60 vs. PND21. Data are quoted as the mean ± SEM, n = 10-12/group.</p

Effects of CPF exposure on the body weight of rat pups at birth (PND01, open bars), as juveniles (PND21, grey bars) and as young adults (PND60, black bars).

<p>Data are quoted as the mean ± SEM, at PND01 and PND21: n = 20-22/group; at PND60, n = 10-12/group. ***: p<0.001.</p

Effects of CPF exposure on respiratory parameters in juvenile rats (PND21 grey bars) and adult rats (PND60, black bars).

<p>(A) T_I (ms), (B) T_E (ms), (C) f (bpm), and (D) V_T (ml/100g body weight) in juvenile and adult rats. Data are quoted as the mean ± SEM, n = 10-12/group. Effect of CPF exposure: *: p<0.05; ***: p<0.001. For a significant age x exposure interaction: #: p<0.05; # # #: p<0.001; $: p<0.1 compared with controls of the same age (<i>unpaired t-test</i>).</p

Effects of CPF exposure on diaphragm contractility in juvenile (PND21, grey bars) and adult (PND60, black bars) rats.

<p>(A) Twitch tension, (B) time to peak, (C) half relaxation time, (D) fatigability index. Effect of CPF exposure: **: p<0.01; ***: p<0.001, $: p<0.1. Data are quoted as the mean ± SEM, n = 10-12/group.</p

Effects of CPF exposure on AChE activity in the diaphragm in juvenile (PND21, grey bars) and adult (PND60, black bars) rats.

<p>**: p<0.01; ***: p<0.001 compared with controls or CPF-1. Data are quoted as the mean ± SEM, n = 10-12/group.</p