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Neurotoxic effects of combined treatment of 2,5-hexanedione and triethyllead chloride.

Abstract
Triethyllead chloride and 2,5-hexanedione are known neurotoxicants that apparently work through separate mechanisms. The effect of combined treatment of triethyllead chloride and 2,5-hexanedione for 6 weeks on Fischer 344 rats was investigated. Ten rats were given 0.7 mg/kg triethyllead chloride in a volume of 2 ml/kg by gavage while another group was given 0.5% 2,5-hexanedione in drinking water and vehicle by gavage (2 ml/kg). A third group was given a combination of the two treatments. A fourth group served as controls and was given vehicle by gavage. 2,5-Hexanedione produced a reversible loss of body weight, decreased grip strength, and decreased horizontal motor activity. Triethyllead chloride alone increased hot-plate latencies. Triethyllead chloride and 2,5-hexanedione treated animals recovered 4 weeks after cessation of treatment. Neither treatment alone produced fatalities. In combination (2,5-hexanedione + triethyllead chloride) decreases in body weight appeared additive and there was a 40% mortality by 6 weeks of dosing. Rats given the combined treatment had significant loss of both grip strength and increased hot-plate latencies. Neurobehavioral deficits and neuropathological changes were greater in the combined treatment with 2,5-HD and TEL than when either chemical was used alone; there was little indication of a synergistic interaction between these two types of neurotoxicants.
AuthorsD M Lapadula, H A Tilson, G Campbell, M B Abou-Donia
JournalJournal of toxicology and environmental health (J Toxicol Environ Health) Vol. 21 Issue 4 Pg. 483-92 ( 1987) ISSN: 0098-4108 [Print] United States
PMID3599091 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Hexanones
  • Ketones
  • Organometallic Compounds
  • triethyllead
  • 2,5-hexanedione
  • NADH Dehydrogenase
Topics
  • Administration, Oral
  • Animals
  • Body Weight (drug effects)
  • Drug Synergism
  • Hexanones (toxicity)
  • Ketones (toxicity)
  • Liver (drug effects, enzymology)
  • Male
  • Motor Activity (drug effects)
  • NADH Dehydrogenase (metabolism)
  • Organometallic Compounds (toxicity)
  • Rats
  • Rats, Inbred F344
  • Reaction Time (drug effects)
  • Sciatic Nerve (drug effects, pathology)

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