Low-level exposure to diquat induces a neurally mediated intestinal hypersecretion in rats: involvement of nitric oxide and mast cells.
Diquat, a nonselective desiccant herbicide, induces a significant secretion of fluid into the lumen of the gastrointestinal tract of rats at sublethal doses (from 0.5 to 50 mg/kg). This study investigated the effect of an acute low-level exposure to diquat (0. 1, 0.5, and 1 mg/kg) on intestinal net water flux and the mechanisms involved. In anesthetized rats, an intestinal loop (7 cm) was infused with Ringer's buffer containing [14C]-polyethylene glycol 4000. After equilibration, diquat (0.1, 0.5, and 1 mg/kg) was added to Ringer's buffer during 60 min. Net water flux was calculated according to [14C] activity determined in the effluent collected at 15-min intervals. Infused in the intestinal loop for 60 min at doses of 0.5 and 1 mg/kg but not at 0.1 mg/kg, diquat induced an intestinal net water secretion during 180 min with a maximal effect at the highest dose used and during the first hour following the end of diquat infusion. Diquat-induced (1 mg/kg) intestinal net water secretion was blocked by a neurotoxin, tetrodotoxin (5 micrograms/kg iv), doxantrazole (5 mg/kg ip), a mast cell stabilizer, and two inhibitors of NO synthases: l-NAME (25 mg/kg ip) and aminoguanidine (2 mg/kg ip). It is concluded that a single low-level (0.5 and 1 mg/kg) intrajejunal administration of diquat induces a net water intestinal secretion and that this secretory effect is nerve-mediated, implying mast cell degranulation and NO release.
Department of Pharmacology and Toxicology, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, B.P. 3, Toulouse, 31931, France.
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P
Anton
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V
Theodorou
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J
Fioramonti
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L
Bueno
D000818:Animals; D001834:Body Water / Q000378:metabolism; D004178:Diquat / Q000633:toxicity*; D017615:Enteric Nervous System / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006540:Herbicides / Q000633:toxicity*; D007419:Intestinal Secretions / Q000187:drug effects*; D007583:Jejunum / Q000294:innervation* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D004791:Enzyme Inhibitors; D006146:Guanidines; D006540:Herbicides; D013892:Thioxanthenes; D044004:Xanthones; D009569:Nitric Oxide; D013779:Tetrodotoxin; D004178:Diquat; C004479:pimagedine; C010134:doxantrazole; D019331:NG-Nitroarginine Methyl Ester