Membrane expansion of intact erythrocytes by anesthetics

Seeman, Philip; Kwant, W.O.; Sauks, T.; Argent, W.

doi:10.1016/0005-2736(69)90163-1

Cited by 125 publications

(29 citation statements)

References 33 publications

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“…A correlation between the hydrophobicity of a compound and its effects on cells was first observed for anesthetics (27)(28)(29), which provided a basis for calculating a dose-effect relationship. In addition, the uncoupling effects of lipophilic compounds on energy transduction have been studied in animal cells (23).…”

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“…Knowledge of the toxic action of lipophilic compounds on bacterial cells is mainly restricted to the relation between the hydrophobicity (13) of a compound and its effect on a specific enzyme (19). In most studies, the cytoplasmic membrane is mentioned as a possible target, but information about the nature of the toxic action is not presented (1,19).A correlation between the hydrophobicity of a compound and its effects on cells was first observed for anesthetics (27)(28)(29), which provided a basis for calculating a dose-effect relationship. In addition, the uncoupling effects of lipophilic compounds on energy transduction have been studied in animal cells (23).…”

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Effects of the membrane action of tetralin on the functional and structural properties of artificial and bacterial membranes

et al. 1992

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Tetralin is toxic to bacterial cells at concentrations below 100 ,mollliter. To assess the inhibitory action of tetralin on bacterial membranes, a membrane model system, consisting of proteoliposomes in which beef heart cytochrome c oxidase was reconstituted as the proton motive force-generating mechanism, and several gram-positive and gram-negative bacteria were studied. Because of its hydrophobicity, tetralin partitioned into lipid membranes preferentially (lipid/buffer partition coefficient of tetralin is approximately 1,100). The excessive accumulation of tetralin caused expansion of the membrane and impairment of different membrane functions. Studies with proteoliposomes and intact cells indicated that tetralin makes the membrane permeable for ions (protons) and inhibits the respiratory enzymes, which leads to a partial dissipation of the pH gradient and electrical potential. The effect of tetralin on the components of the proton motive force as well as disruption of protein-lipid interaction(s) could lead to impairment of various metabolic functions and to low growth rates. The data offer an explanation for the difficulty in isolating and cultivating microorganisms in media containing tetralin or other lipophilic compounds.Interest in the application of water-immiscible organic compounds in fermentations has increased in the last decade. Many lipophilic compounds are harmful to microorganisms, impair growth, and even inhibit other biological reactions. Knowledge of the toxic action of lipophilic compounds on bacterial cells is mainly restricted to the relation between the hydrophobicity (13) of a compound and its effect on a specific enzyme (19). In most studies, the cytoplasmic membrane is mentioned as a possible target, but information about the nature of the toxic action is not presented (1,19).A correlation between the hydrophobicity of a compound and its effects on cells was first observed for anesthetics (27)(28)(29), which provided a basis for calculating a dose-effect relationship. In addition, the uncoupling effects of lipophilic compounds on energy transduction have been studied in animal cells (23). For microorganisms, only a few studies on the toxic effects of lipophilic compounds on various membrane functions have been performed (3,32,33). These studies showed that hydrocarbons, e.g., 3-pinene (32) and cyclohexane (33), impaired energy transduction in both mitochondrial and plasma membranes of yeast cells. Studies on the toxic effects of ethanol on yeast cells indicated that the Ap across the plasma membrane was dissipated in the presence of ethanol (3), probably due to an increased influx of protons (3,12).In this investigation, the toxic action of the lipophilic compound tetralin on bacteria was studied. Tetralin was found to be toxic to bacterial cells at concentrations below 100 ,umol/liter (30). Tetralin, 1,2,3,4-tetrahydronaphthalene, is a bicyclic molecule that consists of an aromatic and an alicyclic moiety. The compound is widely applied as an industrial solvent and as a substitute f...

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Effects of the membrane action of tetralin on the functional and structural properties of artificial and bacterial membranes

et al. 1992

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“…For example, the critical volume at which the erythrocyte membrane undergoes osmotic hemolysis (14) is increased by the alcohols and by volatile general anesthetics (15). This effect correlates with the extent to which these agents are incorporated into the erythrocyte and produce membrane swelling (16). Because incorporation of these agents into the erythrocyte results in hemolysis and incorporation into the nerve membrane results in a loss of excitability, we proposed that hemolysis might be a reliable first-tier assay for screening the neurotoxic potential of organic solvents.…”

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Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

Anderson¹,

Glasgow²,

Dunham³

1984

Environ Health Perspect

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The expense, length of time and number of animals required for routine toxicity testing have provided the incentive for finding alternative techniques which are faster, less expensive and equally valid. The purpose of this work was to examine the value of a simple in vitro test (hemolysis) as a correlate of the neurotoxicity produced by commonly used industrial organic solvents. Incubation of rat erythrocytes with organic alcohols produced hemolysis which correlates with the potency of the same alcohols to suppress membrane excitability, measured as reduction in the evoked action potential of the rat sciatic nerve. The hemolytic activity also reflects changes in water solubility among the compounds and thus can be used as an index of in vivo neurotoxicity, the extent of which partly depends on absorption of the agent and delivery to nerve tissue. Hemolysis therefore may be of value as a preliminary test for assessing the neurotoxicity of organic solvents.

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“…Human erythrocytes are protected or stabilized by a variety of small lipophilic compounds such as anesthetics, tranquilizers, anti-histamines and alcohols (22)(23)(24)(25). Generally, these compounds show biphasic effects.…”

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“…Generally, these compounds show biphasic effects. At relatively low concentrations, these drugs protect erythrocytes from hypotonic hemolysis, but at high concentrations, they promote hemolysis (22)(23)(24)(25). Although the mechanism for this drug-induced antihemolytic effect is not known, the protective effect frequently has been used to study the interaction of these compounds with biological membranes.…”

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