The effect of a neurotoxic organo-metal, methyl mercuric iodide, and an aromatic solvent, toluene, upon the transmembrane potential (psi), across both the limiting membrane of isolated nerve terminals and their mitochondria, has been studied. Exposure of nerve endings to either of these toxicants in vitro resulted in a dose-dependent diminution of psi that was especially pronounced in the case of mitochondria. This was not prevented by a concurrent exposure to an antioxidant (alpha-tocopherol), or an iron chelator (deferoxamine), or ganglioside GM1. No significant changes were detected in synaptosomal potentials derived from cortices of rats exposed to methyl mercury or toluene at levels known to increase the rate of formation of reactive oxygen species within this region. The special vulnerability of mitochondrial psi to these agents may be due to the disruption of oxidative phosphorylation and may be related to the increase in intrasynaptosomal free ionic calcium that both of these chemicals can induce.

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.