title: Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?
abstract: Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation.
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078, USA. jing.pope@okstate.edu
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: John T
authors.initials: JT
authors.lastname: Goad
authors.forename: Subramanya
authors.initials: S
authors.lastname: Karanth
authors.forename: Carey
authors.initials: C
authors.lastname: Pope
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D010278:Parathion / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000227:Adenine Nucleotides; D002800:Cholinesterase Inhibitors; D002956:Citrulline; D009569:Nitric Oxide; D010278:Parathion; D019255:NADPH Oxidases; D002802:Cholinesterases; D005947:Glucose; D003401:Creatine