Structural changes of rat liver microsomal membranes induced by the oral administration of carbon tetrachloride. 31P-NMR and spin-label studies.

The acute effects of carbon tetrachloride (CCl4) on the membrane structure of rat liver microsomes were studied using 31P-NMR and spin-labeling techniques. 31P-NMR spectra of rat liver microsomes were not changed appreciably after the oral administration of CCl4, indicating that the surface structures of microsomal membranes probably are not influenced by the oral administration of CCl4. Four different spin-labeled stearic acids, 5-(N-oxyl-4',4'-dimethyloxazolidine)-stearic acid (5SLS), its methyl ester (5SLSM), 12-(N-oxyl-4',4'-dimethyloxazolidine)-stearic acid (12SLS) and its methyl ester (12SLSM), were used for the estimation of membrane fluidity. The apparent rotational correlation time of 12SLS decreased from 4.0 nsec to 3.0 nsec after the oral administration of CCl4, while the order parameter of 5SLS did not change. The results suggest that CCl4 or its metabolites increase the membrane fluidity of liver microsomes primarily at hydrophobic regions rather than at the surface layer. The ESR spectrum of 5SLSM in microsomal membranes comprised two different signals; one was an anisotropic signal and the other was a rather isotropic one. The ratio of the anisotropic signal to the isotropic one decreased markedly after the oral administration of CCl4 and depended on the dose of CCl4. The suitability of this ESR technique with 5SLSM for the estimation of membrane damage is discussed.