Promethazine protects against 3-nitropropionic acid-induced neurotoxicity. Academic Article uri icon

Overview

MeSH

  • Animals
  • Disease Models, Animal
  • Male
  • Mice
  • Rats
  • Rats, Inbred Lew
  • Succinate Dehydrogenase

MeSH Major

  • Amyotrophic Lateral Sclerosis
  • Brain Ischemia
  • Huntington Disease
  • Neuroprotective Agents
  • Nitro Compounds
  • Promethazine
  • Propionates

abstract

  • Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo. Copyright 2009 Elsevier Ltd. All rights reserved.

publication date

  • January 2010

has subject area

  • Amyotrophic Lateral Sclerosis
  • Animals
  • Brain Ischemia
  • Disease Models, Animal
  • Huntington Disease
  • Male
  • Mice
  • Neuroprotective Agents
  • Nitro Compounds
  • Promethazine
  • Propionates
  • Rats
  • Rats, Inbred Lew
  • Succinate Dehydrogenase

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4634881

Digital Object Identifier (DOI)

  • 10.1016/j.neuint.2009.10.006

PubMed ID

  • 19852992

Additional Document Info

start page

  • 208

end page

  • 212

volume

  • 56

number

  • 2