Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate

E. A. Yount, S. Y. Felten, B. L. O'Connor, R. G. Peterson, R. S. Powell, M. N. Yum, Robert Harris

Research output: Contribution to journalArticle

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Abstract

The metabolic and toxic effects of 2-chloropropionate and dichloroacetate, activators of the pyruvate dehydrogenase complex, were compared. In 4-hr fasted mice, the oral LD50 values for 2-chloropropionate and dichloroacetate were 15.4 ± 0.1 and 32.1 ± 1.1 mmol/kg, respectively. In suckling rats, both compounds effectively lowered blood lactate and glucose levels and increased blood ketone bodies. Although comparable effects were brought about by both compounds on other metabolites, dichloroacetate caused a greater increase in blood ketone bodies. In a prolonged oral toxicity study using male rats, both compounds decreased growth rate and food consumption and caused neurotoxic effects. Both compounds brought about hind limb weakness, slower nerve conduction velocities and decreased diameter of tibial nerves. 2-Chloropropionate treatment caused testicular abnormalities manifested by testicular maturation arrest and degeneration of germ cells. 2-Chloropropionate-treated rats had significantly lower plasma triacylglycerol levels than control or dichloroacetate-treated rats. In mature rats, total serum ketone bodies were increased by dichloroacetate but not significantly elevated by 2-chloropropionate. Although 2-chloropropionate may lack sufficient safety to warrant chronic use in humans, it is a useful research tool for studying the metabolic effects of activation of the pyruvate dehydrogenase complex. Since 2-chloropropionate is not converted to oxalate and is not as ketogenic as dichloroacetate, 2-chloropropionate may be useful clinically in situations requiring only short-term therapy.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume222
Issue number2
StatePublished - 1982
Externally publishedYes

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Poisons
Ketone Bodies
Pyruvate Dehydrogenase Complex
Hairless Mouse
Tibial Nerve
Oxalates
2-chloropropionic acid
Lethal Dose 50
Neural Conduction
Germ Cells
Blood Glucose
Lactic Acid
Triglycerides
Extremities
Safety
Food
Growth
Serum
Research

ASJC Scopus subject areas

  • Pharmacology

Cite this

Yount, E. A., Felten, S. Y., O'Connor, B. L., Peterson, R. G., Powell, R. S., Yum, M. N., & Harris, R. (1982). Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate. Journal of Pharmacology and Experimental Therapeutics, 222(2), 501-508.

Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate. / Yount, E. A.; Felten, S. Y.; O'Connor, B. L.; Peterson, R. G.; Powell, R. S.; Yum, M. N.; Harris, Robert.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 222, No. 2, 1982, p. 501-508.

Research output: Contribution to journalArticle

Yount, EA, Felten, SY, O'Connor, BL, Peterson, RG, Powell, RS, Yum, MN & Harris, R 1982, 'Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate', Journal of Pharmacology and Experimental Therapeutics, vol. 222, no. 2, pp. 501-508.
Yount EA, Felten SY, O'Connor BL, Peterson RG, Powell RS, Yum MN et al. Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate. Journal of Pharmacology and Experimental Therapeutics. 1982;222(2):501-508.
Yount, E. A. ; Felten, S. Y. ; O'Connor, B. L. ; Peterson, R. G. ; Powell, R. S. ; Yum, M. N. ; Harris, Robert. / Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate. In: Journal of Pharmacology and Experimental Therapeutics. 1982 ; Vol. 222, No. 2. pp. 501-508.
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