Prevention of chemically induced synaptosomal changes

Abstract

The ability of altered environmental conditions to modulate some properties of synaptosomes has been studied. Incubation conditions used included the presence of methyl mercury or an organochlorine insecticide: chlordecone. Other adverse chemical conditions during incubation were the absence of calcium salts from the incubation medium or the addition of agents bringing about enhanced oxidative conditions. Synaptosomal parameters studied were the cytosolic level of free, ionic calcium, [Ca2+]i, the extent of depolarization-induced uptake of radioactive calcium, and the permeability of the limiting membrane. In addition, peroxidative activity was estimated by quantitation of thiobarbituric acid-reactive material. All these facets of synaptosomal function were responsive to the presence of these potentially deleterious changes in the incubation medium. While the response of [Ca2+]i was potentially in either direction, all adverse conditions increased synaptosomal permeability as evaluated by leakage of fura-2 into the extracellular compartment. Pretreatment with ganglioside GM1 in some situations or alpha-tocopherol in others could either wholly or partially prevent the onset of such altered synaptosomal characteristics.

Deferoxamine inhibits methyl mercury-induced increases in reactive oxygen species formation in rat brain

“…Studies have reported that MeHg 1 This work was supported by NIH Grants ES 04071 and ES 07157. 161 stimulates lipid peroxidation (Yonaha et al, 1983) and the lipoperoxidative effects of MeHg are mitigated by the antioxidant a-tocopherol (vitamin E; Halliwell and Gutteridge, 1985;Kasuya, 1975;Bondy and McKee, 1990). Additionally, this laboratory has recently demonstrated that both in vivo and in vitro exposures to MeHg increased the formation rate of reactive oxygen species in mouse brain , effects that were observed only in the cerebellum, the brain region believed to be selectively vulnerable to MeHg (Syverson et al, 1981 ).…”

Effects of toluene and its metabolites on cerebral reactive oxygen species generation

“…Recently, ROS have been reported to play a role in the neurotoxic mechanisms of methylmercury and trimethyltin [17, :j:]. These studies were performed using the fluorescent dyes 2' ,7'-dichlorofluorescein and rhodamine 123, markers that have proven to be more sensitive measures of oxidative stress than the traditional thiobarbituric acid assay [17,18]. A ferryl-ion or peroxo-metal complex may be the reactive species directly responsible for the oxidation of nonfluorescent dichlorofluorescin to highly fluorescent dichlorofluorescein [19].…”

Oxidative damage and cerebral aging

“…Ganglioside GM!, a membrane-stabilizing agent effective within the CNS, may also mitigate some components of oxidative damage to neural tissue. This ganglioside has been reported protective against ischemia (Mahadik et al, 1989), edema (Koga et al, 1990, Skaper et al, 1989, and direct oxidative activity (Bondy and McKee, 1990). The therapeutic application of macromolecular proteins as a means of reducing ROS production is obviously somewhat limited.…”