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Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.

Publication ,  Journal Article
Qiao, D; Seidler, FJ; Slotkin, TA
Published in: Toxicol Appl Pharmacol
August 1, 2005

Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults.

Duke Scholars

Published In

Toxicol Appl Pharmacol

DOI

ISSN

0041-008X

Publication Date

August 1, 2005

Volume

206

Issue

1

Start / End Page

17 / 26

Location

United States

Related Subject Headings

  • Vitamin E
  • Toxicology
  • Thiobarbituric Acid Reactive Substances
  • Rats, Sprague-Dawley
  • Rats
  • Oxidative Stress
  • Nicotine
  • Lipid Peroxidation
  • Ganglionic Stimulants
  • Drug Interactions
 

Citation

APA
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ICMJE
MLA
NLM
Qiao, D., Seidler, F. J., & Slotkin, T. A. (2005). Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos. Toxicol Appl Pharmacol, 206(1), 17–26. https://doi.org/10.1016/j.taap.2004.11.003
Qiao, Dan, Frederic J. Seidler, and Theodore A. Slotkin. “Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol 206, no. 1 (August 1, 2005): 17–26. https://doi.org/10.1016/j.taap.2004.11.003.
Qiao D, Seidler FJ, Slotkin TA. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos. Toxicol Appl Pharmacol. 2005 Aug 1;206(1):17–26.
Qiao, Dan, et al. “Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicol Appl Pharmacol, vol. 206, no. 1, Aug. 2005, pp. 17–26. Pubmed, doi:10.1016/j.taap.2004.11.003.
Qiao D, Seidler FJ, Slotkin TA. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos. Toxicol Appl Pharmacol. 2005 Aug 1;206(1):17–26.
Journal cover image

Published In

Toxicol Appl Pharmacol

DOI

ISSN

0041-008X

Publication Date

August 1, 2005

Volume

206

Issue

1

Start / End Page

17 / 26

Location

United States

Related Subject Headings

  • Vitamin E
  • Toxicology
  • Thiobarbituric Acid Reactive Substances
  • Rats, Sprague-Dawley
  • Rats
  • Oxidative Stress
  • Nicotine
  • Lipid Peroxidation
  • Ganglionic Stimulants
  • Drug Interactions