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Published on: May 4, 2009
Does pyruvate prevent acrylamide neurotoxicity? Implications for disease pathogenesis
Abstract:
We used the prototype environmental neurotoxin, acrylamide monomer, to evaluate the hypothesis that neurotoxin-induced nerve fiber degeneration results from inactivation of axonal glycolytic enzymes. Treating intoxicated rats with sodium pyruvate, we hypothesized, would bypass the putative neurotoxin-induced blockade in glycolysis, thus ameliorating neurobehavioral and morphologic measures of neurotoxicity. After establishing that pyruvate itself did not affect behavior, we examined its effects on acrylamide-intoxicated animals. Pyruvate treatment had a significant effect on only one of eight neurobehavioral measures, though others showed similar trends. A morphologic observation of lumbar dorsal root ganglion cell bodies and peripheral nerves failed to show an effect of pyruvate. Those results suggested that inactivation of glycolytic enzymes alone is not a sufficient explanation of pathogenesis.
Insights
This study investigated if blocking glycolysis causes nerve damage from acrylamide. Treating rats with sodium pyruvate did not significantly prevent acrylamide neurotoxicity, suggesting other mechanisms are involved.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Acrylamide monomer is a neurotoxin that causes nerve fiber degeneration.
- The hypothesis is that this degeneration results from inactivation of axonal glycolytic enzymes.
Purpose of the Study:
- To evaluate the hypothesis that neurotoxin-induced nerve fiber degeneration results from inactivation of axonal glycolytic enzymes.
- To determine if sodium pyruvate can ameliorate acrylamide neurotoxicity by bypassing glycolysis blockade.
Main Methods:
- Rats were intoxicated with acrylamide monomer.
- Treated intoxicated rats with sodium pyruvate.
- Assessed neurobehavioral and morphologic measures of neurotoxicity.
- Established that pyruvate alone did not affect behavior.
Main Results:
- Pyruvate treatment significantly affected only one of eight neurobehavioral measures in acrylamide-intoxicated rats.
- Other neurobehavioral measures showed similar trends but were not statistically significant.
- Morphologic examination of dorsal root ganglion cell bodies and peripheral nerves showed no effect of pyruvate.
Conclusions:
- Inactivation of glycolytic enzymes alone is not a sufficient explanation for acrylamide-induced neurotoxicity.
- Further research is needed to elucidate the complete pathogenesis of acrylamide neurotoxicity.
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