Soman poisoning alters p38 MAPK pathway in rat cerebellar Purkinje cells

J Appl Toxicol. 2009 May;29(4):338-45. doi: 10.1002/jat.1415.

Abstract

The aim of the study was to evaluate the expression of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated transcription factors elk-1, c-jun and c-myc in rat cerebellar Purkinje cells after soman poisoning to investigate the pathogenetic mechanism of non-specific long-term adverse effects of nerve agents. Male Wistar rats were poisoned by intramuscular administration of soman at a dose 60 microg kg(-1) (80% LD(50)), while control animals were administered physiological saline. Samples were taken 1, 7 and 14 days after poisoning, immunohistochemically stained and p-p38MAPK, p-c-jun, p-c-myc, and p-elk-1 expressions were measured using computer image analysis. An increased expression of phosphorylated p38 MAPK and c-myc 14 days after soman poisoning was found, while both activated elk-1 and c-jun expression remained unchanged 1, 7 and 14 days after intoxication. Late activation of p38 MAPK and their targets might be the underlying mechanism of chronic neurophysiological adverse effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / cytology
  • Cerebellum / drug effects*
  • Cerebellum / pathology
  • Cholinesterase Inhibitors / poisoning*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Male
  • Nerve Tissue Proteins / biosynthesis
  • Phosphorylation
  • Purkinje Cells / drug effects*
  • Purkinje Cells / pathology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Soman / poisoning*
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / physiology*

Substances

  • Cholinesterase Inhibitors
  • Nerve Tissue Proteins
  • Transcription Factors
  • Soman
  • p38 Mitogen-Activated Protein Kinases