Ganglioside GM1 prevents and reverses toluene-induced increases in membrane fluidity and calcium levels in rat brain synaptosomes

Euler, Gabriel von; Fuxé, Kjell; Bondy, Stephen C.

doi:10.1016/0006-8993(90)90398-u

Cited by 41 publications

(21 citation statements)

References 37 publications

(7 reference statements)

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“…1). Equivalent concentrations of toluene have been shown not to dramatically affect membrane permeability (von Euler et al, 1990). In addition, an equivalent in vitro exposure to benzene, a structurally related organic solvent with no known neurotoxic potential, did not alter the rate of generation of Fig.…”

Section: Resultsmentioning

confidence: 96%

“…Recent studies have indicated that toluene neurotoxicity may be expressed through a membrane-associated event, such as, alteration of membrane fluidity and levels of intracellular Cat and Cat+-regulated events Schatz, 1989, 1990;von Euler et al, 1990). Toluene has been shown to induce morphological changes in astroglia and neurons in striatal primary cell cultures .…”

Section: Introductionmentioning

confidence: 99%

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Toluene-induced oxidative stress in several brain regions and other organs

Mattia

Ali

Bondy

1993

Molecular and Chemical Neuropathology

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Toluene-induced oxidative stress in several brain regions and other organs

Mattia

Ali

Bondy

1993

Molecular and Chemical Neuropathology

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“…Animal studies have suggested that extended toluene exposure may induce long-lasting morphological changes in the frontal cortex [2] and hippocampal and cerebellar regions (3). Studies on specific biochemical changes effected by toluene have reported neuronal membrane alterations involving enhanced Ca2+ /Mt+ ·ATPase activity (4], increased intracellular Ca+ [5] and membrane fluidity (6], and alterations in receptor binding and neurotransmitter content [2].…”

mentioning

confidence: 99%

Free radical induction in the brain and liver by products of toluene catabolism

Mattia

Adams

Bondy

1993

Biochemical Pharmacology

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Abstract-Toluene and its metabolites have been studied with respect to their reactive oxygen speciesenhancing potential in isolated systems and in vivo. The induction of reactive oxygen species (ROS) production was assayed using the probe 2' ,7' -dichlorodihydroftuorescin diacetate (DCFH-DA). Intraperitoneal injection of toluene, benzyl alcohol or benzaldehyde caused a significant elevation in the rate of ROS formation within hepatic mitochondrial fractions (P2). In the brain, only toluene induced ROS formation, while benzyl alcohol and benzaldehyde did not have any effect. Glutathione (GSH) levels were depressed in liver and brain regions from toluene-treated rats. However, no such depression was evident in brains treated with toluene metabolites. P2 fractions from phenobarbital-pretreated rats exhibited a heightened ROS response when challenged with toluene, in vitro. Pretreatment of rats in vivo with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, or sodium cyanamide, an aldehyde dehydrogenase inhibitor, prior to exposure to toluene, caused a significant decrease and increase, respectively, in toluene-stimulated rates of ROS generation in the CNS and liver. Electron spin resonance spectroscopy, employing the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was conducted. Incubation of the spin trap with P2 fractions and toluene or benzaldehyde elicited a spectrum corresponding to the hydroxyl radical. Incubation of benzaldehyde with aldehyde dehydrogenase produced a strong signal that was blocked completely by superoxide dismutase and inhibited partially by catalase, suggesting the presence of superoxide radicals and the involvement of the iron-catalyzed Haber-Weiss reaction leading to the production of hydroxyl radicals. Thus, ROS generation during toluene catabolism may occur at two steps: cytochrome P450 oxidation and aldehyde dehydrogenase oxidation. In addition, GSH may play an important role in protection against the induction of ROS generation in the CNS and liver following exposure to toluene.

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“…Synaptosomes isolated from toluene-treated rats, and subsequently incubated in toxicant-free HEPES buffer, have normal levels of [Ca 2 +]i although the permeability of the limiting membrane is elevated [Von Euler et al, in preparation]. This differs from results obtained using synaptosomes exposed to toluene in vitro, where these parameters are both elevated [24]. Another possible reason for the apparent resistance of nerve endings to detectable changes following their exposure to neurotoxic agents in vivo is their much higher density per unit of toxicant encountered in the living animal than is the case with isolated tissue fractions.…”

Section: Resultsmentioning

confidence: 99%

“…Exposure to methyl mercury has been found to effect reduction of ATP-generating capacity [26,27]. The elevation of cytosolic calcium, [Ca 2 +];, reported to be effected by both methyl mercury and toluene [19,24,27], may in part be due to the collapse of the mitochondrial potential, leading to release of calcium sequestered within mitochondrial binding sites.…”

Section: Resultsmentioning

confidence: 99%