Article Text

  1. T T Lai1,
  2. N Tang1,
  3. M He1,
  4. C F Bearer1
  1. 1Department of Pediatrics, Rainbow Babies and Children’s Hospital, Cleveland, Ohio, USA


Introduction Inert ingredients in neonatal medications have led to adverse effects including death. Benzyl alcohol, a preservative, has been associated with death, developmental delay and cerebral palsy in neonates. Propylene glycol, a solubiliser in medications, is associated with lactic acidosis, central nervous system depression and seizures.

Objective To show that benzyl alcohol and propylene glycol act similarly to ethanol, inhibiting L1-mediated activation of the ERK1/2 signalling pathway. We have previously shown that ethanol inhibits L1 signal transduction and thus L1-mediated neurite outgrowth. We hypothesise that by exposing neurons to benzyl alcohol and propylene glycol, activation of ERK1/2 decreases.

Methods Cerebellar granule neurons from postnatal day 6 rat pups were plated overnight on poly-l-lysine. Cells were serum starved 3 h before triggering. Benzyl alcohol, propylene glycol and ethanol were added 1 h before triggering. The cells were triggered by clustering L1. At 10 minutes, the cells were placed on ice, scraped and lysed. Lysates were immunoblotted for phospho ERK1/2, then stripped and reblotted for total ERK.

Results Benzyl alcohol and propylene glycol inhibited L1-mediated activation of ERK1/2 by 52% and 39%. Results, however, were not statistically significant, with respective p values of 0.055 and 0.124.

Conclusion Benzyl alcohol and propylene glycol seem to inhibit activation of ERK1/2 similarly to ethanol and subsequently are likely to affect L1-mediated neurite outgrowth. Our small sample size, however, was not statistically significant. With further refinement this assay may allow simple screening to test the safety of inert ingredients in neonatal medications.

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