Effect of Organic Solvents on Nervous Cell Membrane as Measured by Changes in the (Ca²⁺/Mg²⁺) ATPase Activity and Fluidity of Synaptosomal Membrane

Abstract

The effect of various solvents on the central nervous system was studied by using rat brain synaptosomal membranes as an in vitro model. The activity of (Ca2+/Mg2+) ATPase and the membrane fluidity was determined. The alteration of the ATPase activity depended on the physio-chemical characteristics of the solvent in question. Incubation with aliphatic alkanes caused a stimulation of the ATPase activity whereas mixed hydrocarbons as kerosene, white spirit and gasoline inhibited the enzyme. Incubation with chlorinated hydrocarbons caused a biphasic response dependent on the concentration. Oxygen-containing hydrocarbons exhibited various effects as found after incubation with hydrocarbons. The different effects of the solvents on the ATPase activity suggest that the lipophilicity of the solvents is one of more parameters affecting the membrane. Furthermore, the biphasic response following the incubation with chlorinated hydrocarbons indicates that more mechanisms are involved in the enzyme effect. The membrane fluidity is increased with higher concentrations of the solvents. From the results it is concluded that the ATPase activity depends not only on the membrane fluidity and volume, but also on the hydrophilic vicinity of the enzyme molecule.

Synaptic plasma membrane-bound acetylcholinesterase activity is not affected by docosahexaenoic acid-induced decrease in membrane order

“…This finding contrasts with the increased activity of synaptosomal AChE found in rats fed high versus low 18:2/18:3 diets (Foot et al, 1983). Our results also contrast with those of several other studies, where aqueous (Tanii et al, 1995), organic (Edelfors and Ravn-Jonsen, 1992;Engelke et al, 1992) or anesthetic compounds (Ondrias et al, 1983;Sidek et al, 1984;Mazzanti et al, 1986) were shown to alter AChE activity with concomitant changes in DPHdetermined membrane disorder of the SPM. Although it is difficult to account for this discrepancy, it may be considered that these organic molecules were encountered by the acyl chains of the phospholipid bilayer acyl chain as an extrinsic factor, whereas DHA after in vivo administration is intrinsically esterified to the phospholipid glycerol backbone.…”

“…If DHA exerts a similar influence on fluidity in the SPM, it could be expected that DHA would also affect the activity of SPMbound AChE. Alterations of brain synaptic plasma membrane fluidity by ethanol (Tanii et al, 1995), benzene (Engelke et al, 1992), toluene (Edelfors and Ravn-Jonsen, 1992) and several anaesthetics (Ondrias et al, 1983;Sidek et al, 1984;Mazzanti et al, 1986) may influence the activity of SPM-bound enzyme such as AChE. Dietary cholesterol, which inversely relates to membrane fluidity (Hashimoto et al, 1999a,b;Hossain et al, 1999a,b), affects synaptosomal AChE activity (Sanchez-Yague et al, 1991).…”

Effects and mechanisms of kerosene use-related toxicity

“…The inhibition of acetylcholinesterase in the trachea of guinea pigs with induction of severe hyper-reactivity of the smooth muscles of the airways as reported by Casaco et al [54] may provide a plausible mechanism for hypoxiainduced consequences on the CNS. Another alternative mechanism on the hypoxia-induced neurotoxicity emanates from studies conducted by Edelfors and Ravn-Jonsen [55] who used in vitro rat CNS synaptasomal membranes exposed to kerosene to show that organic solvents such as kerosene resulted in reduced activity of the enzyme (Ca 2+/ Mg 2+ ) ATPase and subsequently increased levels of intracellular Ca 2+ with a concomitant increase in neurotransmitter release. So far, animal-based studies on kerosene-induced neurotoxicity are inadequate and generally inconclusive [49].…”

The Effect of in vitro Exposure to White Spirit on [Ca2+i] in Synaptosomes from Rats Exposed Prenatally to White Spirit

“…In animal studies, long term exposure to white spirit and toluene (Korbo et al 1996) caused neurophysiological and morphological changes in rat brains even six month after exposure. In vitro experiments have shown that exposure to organic solvents affects biochemical parameters such as membrane fluidity, membrane ATPase activity and intracellular Ca2+ (BeaugC et al 1984;Korpela 1988;Benaim & de Meis 1989;Tahti & Valaja 1991;Edelfors & Ravn-Jonsen 1992). The calcium homeostasis is less well maintained as life progresses, and as a result of age leads to a higher concentration of intracellular free calcium (Sastrustegui et al 1991;Villalba et al 1995).…”