Organometal-induced increases in oxygen reactive species: the potential of 2',7'-dichlorofluorescin diacetate as an index of neurotoxic damage.
The effects of the neurotoxic metals methylmercury (MeHg) and trimethyltin (TMT) on oxygen reactive species formation within a crude synaptosomal fraction (P2), using the probe 2',7'-dichlorofluorescin diacetate (DCFH-DA), and intracellular calcium ([Ca2+]i), with the fluorescent indicator fluo-3, have been investigated. Two and seven days after a single injection of MeHg (1 mg/kg) the formation rate of cerebellar oxygen reactive species was significantly increased. Hippocampal and frontocortical oxygen reactive species were elevated 2 days after TMT injection (3 mg/kg). In vitro exposure to MeHg (10-20 microM) increased the formation rate of oxygen reactive species, while TMT (5-40 microM) was without effect. Levels of [Ca2+]i were unaltered in P2 fractions from cerebellum and hippocampus of animals treated with either organometal. The data demonstrate that oxygen reactive species are elevated in brain regions, cerebellum (MeHg) and hippocampus (TMT), believed to be selectively vulnerable to these toxic agents. Findings suggest that oxidative damage may be a mechanism underlying the toxicity of both organometals. The use of DCFH-DA may have potential in the nervous system as an indicator of neurotoxic damage.
LeBel
C P
CP
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Ali
S F
SF
McKee
M
M
Bondy
S C
SC
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism*; D005609:Free Radicals; D006624:Hippocampus / Q000187:drug effects; D006861:Hydrogen Peroxide; D006878:Hydroxides; D017665:Hydroxyl Radical; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects*; D010100:Oxygen / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D005452:Fluoresceins; D005609:Free Radicals; D006878:Hydroxides; D008767:Methylmercury Compounds; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; D013481:Superoxides; C046488:trimethyltin; C029569:diacetyldichlorofluorescein; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D010100:Oxygen; D002118:Calcium