Propylene glycol produces excessive apoptosis in the developing mouse brain, alone and in combination with phenobarbital

Pediatr Res. 2012 Jan;71(1):54-62. doi: 10.1038/pr.2011.12.

Abstract

Introduction: Propylene glycol (PG) is a common solvent used in medical preparations. It is generally recognized as safe at regulated concentrations; however, its apoptotic potential is unknown.

Results: PG triggered widespread apoptotic neurodegeneration with the greatest damage at postnatal day 7 (P7). Significant apoptosis was observed at doses as low as 2 ml/kg. These findings have implications for the safety of drug preparations used in pediatric medicine. The anticonvulsant phenobarbital (PB), which alone produces apoptosis in the immature central nervous system (CNS) is prepared in 68% PG and 10% ethanol (EtOH). We assessed whether PG contributes to the neurotoxic potential of PB. The agents (both at subtoxic doses) produce significantly more apoptosis when used in combination.

Discussion: In conclusion, finding an alternative non-apoptotic solvent that can be used as a substitute for PG may be beneficial to patients.

Methods: C57BL/6 mice (P4-30) were exposed to PG to examine whether PG could produce apoptosis in the developing CNS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Apoptosis / drug effects*
  • Brain* / drug effects
  • Brain* / growth & development
  • Brain* / pathology
  • Caspase 3 / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Phenobarbital / pharmacology*
  • Propylene Glycol / pharmacology*
  • Solvents / pharmacology*

Substances

  • Anticonvulsants
  • Solvents
  • Propylene Glycol
  • Caspase 3
  • Phenobarbital