High concentrations of dichloroacetate have minor effects on the vitality of the mammalian nerve fibers: an ex-vivo electrophysiological study.

Kagiava A, Theophilidis G.

SOURCE PUBMED LINK: HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/21183852

Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University, Thessaloniki, Greece.

ABSTRACT

Although peripheral neuropathy caused by dichloroacetate has been reported, it has been widely used in the treatment of cancer and genetic mitochondrial illnesses. In this work, a rat’s isolated sciatic nerve was used to explore the acute effects of sodium dichloroacetate on the peripheral nerve fibers. To verify that the nerve fibers are working correctly, the amplitude of the evoked nerve compound action potential (CAP) was evaluated. The nerve fibers had been cultured in normal saline, and the half-vitality time—the amount of time needed to reduce the CAP to 50% of its initial value—was 30.4 0.26 h (n=12). The IT50 was 29.7 0.34 h (n=8) when the nerve fibers were incubated in 10 mmol/l of dichloroacetate, with no discernible difference from the control (P>0.05). The remarkable tolerance of peripheral nerve fibers to dichloroacetate is demonstrated by the fact that a concentration of dichloroacetate as high as 10 mmol/l had no impact on the parameters of the evoked CAP. Dichloroacetate was tested at a concentration of 20 mmol/l, and a 15.2 1.25% (n=12) inhibition in the CAP amplitude resulted. However, even though a small population of nerve fibers became inactive, the viability of the remaining active axons was unaffected, with a final IT50 of 28.1 0.64 h (n=12), with no significant difference from the IT50 of the control, which for This mild effect, with a 15.2 1.25 percent decrease in CAP amplitude, implies that within the sciatic nerve preparation’s 28–30 hour exposure limit, there may be a progressive emergence of certain biochemical alterations that may result in the early phases of dichloroacetate–induced neurotoxicity.

PMID:

21183852

[PubMed – indexed for MEDLINE]

MESH TERMS, SUBSTANCES

MeSH Terms

• Action Potentials/drug effects*
• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/toxicity*
• Axons/drug effects*
• Dichloroacetate/pharmacology
• Dichloroacetate/toxicity*
• Evoked Potentials/drug effects*
• Male
• Nerve Fibers/drug effects*
• Nerve Fibers/physiology
• Rats
• Sciatic Nerve/drug effects*
• Sciatic Nerve/physiology

Substances

• Antineoplastic Agents
• Dichloroacetate

LINKOUT – MORE RESOURCES

Full Text Sources

• Lippincott Williams & Wilkins
• Ovid Technologies, Inc.
• Swets Information Services

Molecular Biology Databases

• DICHLOROACETIC ACID – HSDB