5-doxylstearate and Alcoholism

Chronic ethanol consumption has been shown to affect physical properties of membranes from animals as measured by electron spin resonance (ESR). This study compared for the first time the physical properties of erythrocyte membranes of alcoholic patients and control subjects using ESR procedures. Membrane fluidity was determined in the presence and absence of ethanol using the 5-doxyl stearic acid spin-label. Temperature-dependent phase transition also was determined, as were comparisons between ESR parameters, at the 1st and 5th week after alcohol withdrawal. Ethanol-induced fluidity was significantly greater in membranes of control subjects compared with alcoholic patients. Baseline fluidity did not differ and the temperature at which the phase transition occurred was not significantly different between the two groups. The resistance of membranes of alcoholic patients to fluidization by ethanol was unchanged after 5 weeks of withdrawal. Comparisons between ethanol-induced fluidization at the 1st and 5th week after withdrawal were not significantly different. These studies demonstrate differences in ethanol-induced fluidization between alcoholic patients and control subjects that are consistent with earlier ESR studies using an animal model.

Topics: Adult; Alcoholism; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane; Ethanol; Humans; Male; Membrane Fluidity; Middle Aged; Spin Labels; Time Factors

Using the spin probe 5-doxylstearic acid, we studied the structural perturbations of rat liver mitochondrial membranes produced by exposure to ethanol in vitro and by chronic ethanol feeding. The addition of ethanol in vitro to mitochondria from control animals appears to "fluidize" the membranes, as evidenced by a pronounced decrease in the order parameter. By contrast, in membranes from rats fed ethanol chronically, there was no effect on the order parameter. This resistance of the mitochondrial membranes from chronically intoxicated animals to the fluidizing effect of ethanol probably results from a change in the composition of the phospholipids, because the same differential response to ethanol was observed upon using vesicles of mitochondrial phospholipids extracted from control and chronically treated rats. In the presence of 0.025--0.1 M ethanol, a range that prevails in the blood of chronic alcoholics, the order parameter of mitochondrial membranes from rats fed ethanol was comparable to that of control membranes without ethanol in vitro. Analysis of extracted mitochondrial phospholipids showed that the cardiolipin from ethanol-fed animals had fatty acyl residues that are more saturated than those of controls. These findings point to the underlying molecular mechanism of our previous observation that mitochondria from chronic alcoholic rats are more resistant to uncoupling by ethanol at physiological temperature [Rottenberg, H., Robertson, D. E. & Rubin, E. (1980) Lab. Invest. 42, 318--326]. We suggest that an adaptive change in the phospholipid composition leads to structural alterations, which result in increased resistance to disruption of mitochondrial membranes by ethanol. These changes in lipid composition and structure may explain many, if not all, of the mitochondrial abnormalities that have been previously reported to result from chronic ethanol intoxication.

Topics: Alcoholism; Animals; Cyclic N-Oxides; Disease Models, Animal; Electron Spin Resonance Spectroscopy; Ethanol; Humans; Intracellular Membranes; Liposomes; Male; Membrane Lipids; Mitochondria, Liver; Phospholipids; Rats; Spin Labels