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 language | English (US) |
|---|---|
| Pages (from-to) | 249-256 |
| Number of pages | 8 |
| Journal | Neurotoxicology |
| Volume | 10 |
| Issue number | 2 |
| State | Published - 1989 |
| Externally published | Yes |
Keywords
- 2,5-Hexanedione
- Acrylamide
- Brain Energy Metabolism
- Mitochondrial Respiration
ASJC Scopus subject areas
- Neuroscience(all)
- Toxicology