Impact of prenatal and postnatal exposure to the pesticide chlorpyrifos on the contraction of rat ileal muscle strips: involvement of an inducible nitric oxide synthase‐dependent pathway

Background Prenatal/postnatal exposure to insecticides has been linked to developmental disorders in adulthood. Chlorpyrifos (CPF) is a widely used organophosphorus acetylcholinesterase (AChE)‐inhibiting insecticide. The present study established whether prenatal and postnatal exposure to CPF is ass...

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Published in:Neurogastroenterology and motility 2017-02, Vol.29 (2), p.np-n/a
Main Authors: Darwiche, W., Delanaud, S., Dupont, S., Ghamlouch, H., Ramadan, W., Joumaa, W., Bach, V., Gay‐Quéheillard, J.
Format: Article
Language:English
Subjects:
acetylcholine
Animals
Animals, Newborn
chlorpyrifos
Chlorpyrifos - toxicity
Enzyme Inhibitors - pharmacology
Female
gastrointestinal motility
Gastrointestinal Transit - drug effects
Gastrointestinal Transit - physiology
Ileum - drug effects
Ileum - enzymology
Life Sciences
Male
Muscle Contraction - drug effects
Muscle Contraction - physiology
Muscle, Smooth - drug effects
Muscle, Smooth - enzymology
Nitric Oxide Synthase Type II - antagonists & inhibitors
Nitric Oxide Synthase Type II - biosynthesis
Organ Culture Techniques
perinatality
Pesticides - toxicity
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced
Prenatal Exposure Delayed Effects - physiopathology
Rats
Rats, Wistar
Signal Transduction - drug effects
Signal Transduction - physiology
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Summary:Background Prenatal/postnatal exposure to insecticides has been linked to developmental disorders in adulthood. Chlorpyrifos (CPF) is a widely used organophosphorus acetylcholinesterase (AChE)‐inhibiting insecticide. The present study established whether prenatal and postnatal exposure to CPF is associated with intestinal motor dysfunction in adult rats. Methods Three groups of pregnant rats were exposed to either CPF (1 or 5 mg/kg/day; the CPF1 and CPF5 groups) or vehicle (the control group) by gavage from gestational day 1 until weaning. At weaning, the pups were separated from their dams and individually gavaged (with the same dose) until postnatal day 60. We then measured in vivo intestinal transit and the in vitro contractile responses of ileal smooth muscle strips to electrical field stimulation. Expression of inducible nitric oxide synthase (iNOS) in the ileum was determined using qRT‐PCR and immunoblots. Morphometry and AChE assays were also performed. Key Results At adulthood, the mean body mass was lower in the CPF1 and CPF5 groups than in controls. CPF5 exposure was associated with weaker in vitro contraction of ileal muscle strips, which was reversed by adding the NOS inhibitor (L‐NAME). There was no significant intergroup difference in the mean in vivo transit time. Exposure to CPF was associated with greater iNOS expression, lower AChE activity and reduced circular and longitudinal smooth muscle thickness. Conclusions & Inferences Prenatal and postnatal exposure to CPF in the rat is associated with weaker contraction of ileal longitudinal smooth muscle via a nitrergic mechanism with increased iNOS expression. The present study showed that the exposure to chlorpyrifos (CPF), a widely used insecticide, from the first day of gestation to early adulthood, in a rat model, is associated with low EFS‐induced ileal contraction, elevated iNOS expression, partial inhibition of AChE activity, and low ileal muscle thickness.
ISSN:1350-1925
1365-2982
DOI:10.1111/nmo.12918