title: 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.
abstract: 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.
  
  
  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
  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.
authors.affiliation: PériTox, Périnatalité & Risques Toxiques, UMR-I 01 INERIS, Université de Picardie Jules Verne, Amiens, France.|PhyToxE, PhysioToxicité Environnementale, Lebanese University, Nabatieh, Lebanon.
authors.forename: W
authors.initials: W
authors.lastname: Darwiche
authors.affiliation: PériTox, Périnatalité & Risques Toxiques, UMR-I 01 INERIS, Université de Picardie Jules Verne, Amiens, France.
authors.forename: S
authors.initials: S
authors.lastname: Delanaud
authors.affiliation: EA4666, LNPC, Université de Picardie Jules Verne, Amiens, France.
authors.forename: S
authors.initials: S
authors.lastname: Dupont
authors.affiliation: EA4666, LNPC, Université de Picardie Jules Verne, Amiens, France.
authors.forename: H
authors.initials: H
authors.lastname: Ghamlouch
authors.affiliation: PhyToxE, PhysioToxicité Environnementale, Lebanese University, Nabatieh, Lebanon.|Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Beirut, Lebanon.
authors.forename: W
authors.initials: W
authors.lastname: Ramadan
authors.affiliation: PhyToxE, PhysioToxicité Environnementale, Lebanese University, Nabatieh, Lebanon.
authors.forename: W
authors.initials: W
authors.lastname: Joumaa
authors.affiliation: PériTox, Périnatalité & Risques Toxiques, UMR-I 01 INERIS, Université de Picardie Jules Verne, Amiens, France.
authors.forename: V
authors.initials: V
authors.lastname: Bach
authors.affiliation: PériTox, Périnatalité & Risques Toxiques, UMR-I 01 INERIS, Université de Picardie Jules Verne, Amiens, France.
authors.forename: J
authors.initials: J
authors.lastname: Gay-Quéheillard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004390:Chlorpyrifos / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D007082:Ileum / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010575:Pesticides / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D010575:Pesticides; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D004390:Chlorpyrifos
keywords: acetylcholine; chlorpyrifos; gastrointestinal motility; perinatality