Neurotoxic potential of depleted uranium effects in primary cortical neuron cultures and in Caenorhabditis elegans.
Depleted uranium (DU) is an extremely dense metal that is used in radiation shielding, counterbalances, armor, and ammunition. In light of the public concerns about exposure to DU and its potential role in Gulf War Syndrome (GWS), this study evaluated the neurotoxic potential of DU using focused studies on primary rat cortical neurons and the nematode Caenorhabditis elegans. We examined cell viability, cellular energy metabolism, thiol metabolite oxidation, and lipid peroxidation following exposure of cultured neurons to DU, in the form of uranyl acetate. We concurrently evaluated the neurotoxicity of uranyl acetate in C. elegans using various neuronal-green fluourescent protein reporter strains to visualize neurodegeneration. Our studies indicate that uranyl acetate has low cytotoxic potential, and uranium exposure does not result in significant changes in cellular energy metabolism, thiol metabolite oxidation, or lipid peroxidation. Furthermore, our C. elegans studies do not show any significant neurodegeneration following uranyl acetate exposure. Together, these studies suggest that DU, in the form of uranyl acetate, has low neurotoxic potential. These findings should alleviate the some of public concerns regarding DU as an etiologic agent of neurodegenerative conditions associated with GWS.
Jiang
George C-T
GC
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Tidwell
Kristen
K
McLaughlin
Beth Ann
BA
Cai
Jiyang
J
Gupta
Ramesh C
RC
Milatovic
Dejan
D
Nass
Richard
R
Aschner
Michael
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects*; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009942:Organometallic Compounds; C005460:uranyl acetate; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide