The effects of the wood preservative copper dimethyldithiocarbamate in the hippocampus of maternal and newborn Long-Evans rats.
The potential toxic effects on human health and deleterious effects to the environment by copper dimethyldithiocarbamate (CDDC), an alternative wood preservative to chromated copper arsenate (CCA) have not been investigated. This study describes the neurotoxicity and accumulation of copper in the hippocampus of maternal and newborn Long-Evans rats following a subacute exposure to CDDC. Pregnant rats (220-270g) were treated daily with 0mg/kg, 25mg/kg, 50mg/kg, or 75mg/kg CDDC by oral gavage starting from day 6 of gestation and continuing to parturition. Following parturition, maternal and newborn rats were euthanized and brain tissues were removed, processed, and stored for analysis. Electron microscopy revealed demyelination and by-products of peroxidative damage in treated maternal hippocampi. Treated newborn hippocampi exhibited numerous degenerating mitochondria, membrane bound inclusion bodies, and vacuoles containing degraded structures. Graphite furnace atomic absorption spectrophotometry (GFAAS) demonstrated a significant increase in copper concentration in the tissues of treated animals as compared to controls. Western blot analysis revealed an induction of stress proteins HO-1 and Hsp70 and the formation of 4-hydroxy-2-nonenal (4HNE) adducts. CDDC was shown to be toxic to the brains, at all doses used and this toxicity is attributable to copper-induced lipid peroxidation.
Scharf
Brian
B
Department of Biological Sciences, St. John's University, Queens, NY, USA.
Trombetta
Louis David
LD
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004125:Dimethyldithiocarbamate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015227:Lipid Peroxidation; D008431:Maternal-Fetal Exchange; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D014934:Wood
D000447:Aldehydes; D004125:Dimethyldithiocarbamate; D018840:HSP70 Heat-Shock Proteins; D009942:Organometallic Compounds; C063940:bis(dimethyldithiocarbamate)Cu (II) complex; D003300:Copper; D051547:Heme Oxygenase-1; C027576:4-hydroxy-2-nonenal