The protective effects of zinc on diethyldithiocarbamate cytotoxicity on rat astrocytes in vitro.
The neurotoxicity of diethyldithiocarbamate (DDC) has been documented for decades. In particular, cytotoxic effects against rat astrocytes have been noted by a decrease in cell viability and numerous ultrastructural defects. This study indicates an in vitro protective effect by zinc administration prior to DDC insult. Cell groups pre-treated with 50 microM ZnCl2 prior to the addition of 35 microg/ml DDC showed significant protection when compared with cells treated with DDC alone. Zinc reduced the DDC-mediated toxicity to astrocytes as indicated by an increase in cell adherence and viability. Morphological evaluation indicated a significant decrease in ultrastructural alterations. Metallothionein (MT), a metal regulatory protein known to be induced by zinc was studied to determine its role in this mechanism of protection. Immunocytochemistry and immunoblots showed increased presence of MT in all zinc treated groups. This suggests a protective effect against DDC cytotoxicity on rat astrocytes in vitro may be associated with an increase in MT concentration.
Wilson
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College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
Trombetta
L D
LD
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000633:toxicity*; D002712:Chlorides / Q000494:pharmacology; D004050:Ditiocarb / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D008668:Metallothionein / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
D002614:Chelating Agents; D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D008668:Metallothionein; D004050:Ditiocarb; D015032:Zinc