skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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, butmore » 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.« less

Authors:
 [1];  [2];  [2];  [3];  [3]
  1. Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078 (United States). E-mail: jing.pope@okstate.edu
  2. Breathitt Veterinary Center, Murray State University, Hopkinsville, KY 42241 (United States)
  3. Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078 (United States)
Publication Date:
OSTI Identifier:
20976874
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 219; Journal Issue: 2-3; Other Information: DOI: 10.1016/j.taap.2006.11.005; PII: S0041-008X(06)00419-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOSYNTHESIS; BRAIN; CHOLINESTERASE; CITRULLINE; DRINKING WATER; FEEDING; GLUCOSE; INTAKE; MODULATION; NITRIC OXIDE; PARATHION; PHOSPHATES; RATS; TOXICITY

Citation Formats

Liu Jing, Gupta, Ramesh C., Goad, John T., Karanth, Subramanya, and Pope, Carey. Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?. United States: N. p., 2007. Web.
Liu Jing, Gupta, Ramesh C., Goad, John T., Karanth, Subramanya, & Pope, Carey. Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?. United States.
Liu Jing, Gupta, Ramesh C., Goad, John T., Karanth, Subramanya, and Pope, Carey. Thu . "Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?". United States. doi:.
@article{osti_20976874,
title = {Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?},
author = {Liu Jing and Gupta, Ramesh C. and Goad, John T. and Karanth, Subramanya and Pope, Carey},
abstractNote = {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.},
doi = {},
journal = {Toxicology and Applied Pharmacology},
number = 2-3,
volume = 219,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2007},
month = {Thu Mar 15 00:00:00 EDT 2007}
}