Effects of acrylamide and 2,5-hexanedione on brain mitochondrial respiration

C. J. Medrano, R. M. LoPachin

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The effects of acrylamide (ACR) and 2,5-hexanedione (2,5-HD) on brain mitochondrial respiration were assessed. Mitochondria were isolated from whole brains or brain regions of control and neurotoxicant-treated rats. Direct in vitro exposure of isolated brain mitochondria to ACR (1 mM final concentration) had no effect on respiration, whereas direct exposure to 2,5-HD (1 mM final concentration) inhibited state 3 respiration. Chronic treatment of rats with ACR (50 mg/kg/day x 10 days) did not affect respiration of mitochondria isolated from cortex or brainstem. However, in mitochondria from cerebellum of ACR treated rats, pyruvate + oxaloacetic acid (pyr/oaa) supportd oxygen consumption was decreased significantly in both states 3 and 4. In addition, the ADP/O ratio was reduced in this brain structure. In all brain regions of 2,5-HD (400 mg/kg/day x 24 days) intoxicated rats, pyr/oaa supported state 3 respiration was reduced. Glutamate + malate (glu/mal) supported respiration was diminished only in mitochondria isolated from brain stem of 2,5-HD treated rats. In contrast, the non-neurotoxic analogs, 1,6-hexanediol and N,N'-methylene-bis-acrylamide did not alter mitochondrial respiration in parallel experiments. Thus, both ACR and 2,5-HD produce a substrate-dependent, toxicologically specific inhibition of brain mitochondrial respiration. This inhibition of mitochondrial energy production might play a role in the neurotoxic mechanisms of action for these chemicals.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalNeurotoxicology
Volume10
Issue number2
StatePublished - 1989
Externally publishedYes

Keywords

  • 2,5-Hexanedione
  • Acrylamide
  • Brain Energy Metabolism
  • Mitochondrial Respiration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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