Response of rats to low levels of sarin

Rogene F. Henderson, Edward B. Barr, Walter B. Blackwell, Connie R. Clark, Carole A. Conn, Roma Kalra, Thomas H. March, Mohan L. Sopori, Yohannes Tesfaigzi, Margaret G. Ménache, Deborah C Mash

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m3 of sarin for 1 h/day for 1, 5, or 10 days under normal (25°C) and heat-stressed (32°C) conditions were completed and observations were made at 1 day and 1 month after the exposures. The sarin exposures had no observed effects on body weight, respiration rate, and minute volume during exposure nor in body temperature and activity during the 30-day recovery period. There was no evidence of cellular changes in brain determined by routine histopathology nor of any increase in apoptosis. Brain mRNA for interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 was increased in a dose-dependent manner. Autoradiographic studies demonstrated that M1 cholinergic receptor site densities were unchanged at 1 day after repeated exposures with or without heat stress. At 30 days, there was a decrease in M1 receptors in the olfactory tubercle (with and without heat), and, with heat stress, M1 sites also decreased in a dose-dependent manner in the frontal cortex, anterior olfactory nucleus, and hippocampus. M3 receptor sites were not affected by sarin exposure alone. In the presence of heat stress, there was an upregulation in binding site densities in the frontal cortex, olfactory tubercle, anterior nucleus, and striatum immediately after exposure, and these effects persisted at 30 days. Although red blood cell acetylcholinesterase (AChE) was not greatly inhibited by the 1-day exposure, there were 30 and 60% inhibitions after repeated exposures at the low and high doses, respectively. Histochemical staining for AChE demonstrated that sarin exposure alone reduced AChE in the cerebral cortex, striatum, and olfactory bulb. Sarin exposure under heat stress reduced AChE staining in the hippocampus, an area important for memory function. Thus, repeated exposures under heat-stress conditions, to levels of sarin that would not be noticed clinically, resulted in delayed development of brain alterations in cholinergic receptor subtypes that may be associated with memory loss and cognitive dysfunction.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalToxicology and Applied Pharmacology
Volume184
Issue number2
DOIs
StatePublished - Nov 25 2002

Fingerprint

Sarin
Rats
Hot Temperature
Acetylcholinesterase
Brain
Frontal Lobe
Cholinergic Receptors
Hippocampus
Staining and Labeling
Data storage equipment
Inhalation Exposure
Olfactory Bulb
Inbred F344 Rats
Memory Disorders
Respiratory Rate
Body Temperature
Interleukin-1
Cerebral Cortex
Interleukin-6
Blood

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Henderson, R. F., Barr, E. B., Blackwell, W. B., Clark, C. R., Conn, C. A., Kalra, R., ... Mash, D. C. (2002). Response of rats to low levels of sarin. Toxicology and Applied Pharmacology, 184(2), 67-76. https://doi.org/10.1016/S0041-008X(02)99495-0

Response of rats to low levels of sarin. / Henderson, Rogene F.; Barr, Edward B.; Blackwell, Walter B.; Clark, Connie R.; Conn, Carole A.; Kalra, Roma; March, Thomas H.; Sopori, Mohan L.; Tesfaigzi, Yohannes; Ménache, Margaret G.; Mash, Deborah C.

In: Toxicology and Applied Pharmacology, Vol. 184, No. 2, 25.11.2002, p. 67-76.

Research output: Contribution to journalArticle

Henderson, RF, Barr, EB, Blackwell, WB, Clark, CR, Conn, CA, Kalra, R, March, TH, Sopori, ML, Tesfaigzi, Y, Ménache, MG & Mash, DC 2002, 'Response of rats to low levels of sarin', Toxicology and Applied Pharmacology, vol. 184, no. 2, pp. 67-76. https://doi.org/10.1016/S0041-008X(02)99495-0
Henderson RF, Barr EB, Blackwell WB, Clark CR, Conn CA, Kalra R et al. Response of rats to low levels of sarin. Toxicology and Applied Pharmacology. 2002 Nov 25;184(2):67-76. https://doi.org/10.1016/S0041-008X(02)99495-0
Henderson, Rogene F. ; Barr, Edward B. ; Blackwell, Walter B. ; Clark, Connie R. ; Conn, Carole A. ; Kalra, Roma ; March, Thomas H. ; Sopori, Mohan L. ; Tesfaigzi, Yohannes ; Ménache, Margaret G. ; Mash, Deborah C. / Response of rats to low levels of sarin. In: Toxicology and Applied Pharmacology. 2002 ; Vol. 184, No. 2. pp. 67-76.
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