skip to main content

Title: Neurotoxic aspects of porphyinopathies: lead and succinylacetone

Neurotoxic effects of heavy metals and polyhalogenated hydrocarbons frequently occur at low levels of exposure, in some cases below those levels where direct toxic actions of these compounds have been demonstrated. Rats with acute and chronic lead exposure were compared to rats whose heme synthesis was inhibited by succinylacetone, as a semichronic model of the hereditary heme synthesis disorder, acute intermittent porphyria. Both treatments produce significant inhibition in activity of the enzyme delta-aminolevulinic acid dehydrase and elevations in the heme precursor delta-aminolevulinic acid (ALA) in tissues and urine. Associated with increased ALA is a significant inhibition of neurotransmission utilizing the amino acid ..gamma..-aminobutyric acid (GABA), expressed chemically and behaviorally. The results suggest that in addition to their direct molecular neurotoxicity, porphyrinopathic compounds such as lead may, through altering heme synthesis, adversely affect the brain at low levels of exposure.
Authors:
 [1] ; ; ; ;
  1. (National Inst. of Health, Bethesda, MD)
Publication Date:
OSTI Identifier:
5173007
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environ. Res.; (United States); Journal Volume: 29:2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; AMINOLEVULINIC ACID; TOXICITY; BEHAVIOR; PATHOLOGICAL CHANGES; HEME; BIOSYNTHESIS; HYDRO-LYASES; ENZYME ACTIVITY; LEAD; BIOLOGICAL EFFECTS; AMINOBUTYRIC ACID; BRAIN; PORPHYRINS; RATS; AMINO ACIDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARBON-OXYGEN LYASES; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; DRUGS; ELEMENTS; ENZYMES; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; LYASES; MAMMALS; METALS; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PIGMENTS; RODENTS; SYNTHESIS; VERTEBRATES 560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)