Low level lead neurotoxicity in a pregnant guinea pigs model: neuroglial enzyme activities and brain trace metal concentrations.
Specific activities of the astroglial marker glutamine synthetase (GS), and the oligodendroglial marker glycerol-3-phosphate dehydrogenase (GPDH) were measured in the spinal cord of fetal guinea pigs and their dams following chronic exposure to low levels of lead (Pb) during gestation. In addition, the effects of Pb on intracellular trace metals (Cu, Fe, Zn) were measured in the blood, cerebellum and forebrain. Aminolevulinic acid dehydratase (ALAD) and zinc protoporphyrin IX (ZPP) were measured in order to monitor established parameters of Pb-exposure. Pregnant guinea pigs were orally administered 0, 5.5 or 11 mg Pb/kg body weight for 30 or 40 days commencing on day 22 of gestation. Blood Pb levels produced in dams and fetuses were at or near the currently identified "no effect" levels for children (10-30 micrograms/dl). These Pb blood levels produced a significant (P less than 0.05) dose-dependent decrease in GS and GPDH activity in the dams and fetuses. Fe and Zn concentrations in blood, cerebellum and forebrain of both dams and fetuses were significantly (P less than 0.05) decreased in a dose-dependent manner. However, Cu concentrations in the blood, cerebellum and forebrain were decreased in the dams but increased in the fetuses in a dose-dependent fashion. The alteration of trace metal concentrations is a proposed mechanism of Pb neurotoxicity. Blood ALAD activity was significantly (P less than 0.05) decreased and ZPP levels were significantly (P less than 0.05) increased, as expected in Pb-exposed animals. This study presents the first biochemical evidence for the alteration of neuroglial function at low levels of Pb exposure and focuses attention on the fetus as an important Pb target.
Sierra
E M
EM
Department of Veterinary Anatomy, Texas A&M University, College Station 77843.
Rowles
T K
TK
Martin
J
J
Bratton
G R
GR
Womac
C
C
Tiffany-Castiglioni
E
E
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003300:Copper / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006168:Guinea Pigs; D007854:Lead / Q000032:analysis / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology; D000623:Porphobilinogen Synthase / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D011524:Protoporphyrins / Q000097:blood; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology; D014131:Trace Elements / Q000032:analysis*; D015032:Zinc / Q000032:analysis
D011524:Protoporphyrins; D014131:Trace Elements; C017803:zinc protoporphyrin; D007854:Lead; D003300:Copper; D005993:Glycerolphosphate Dehydrogenase; D000623:Porphobilinogen Synthase; D005974:Glutamate-Ammonia Ligase; D015032:Zinc