digitonin and Fatty-Liver

A consensus does not exist regarding the nature of mechanisms linking the initial events of CCl4 metabolism to emergence of the classical indices of CCl4 liver cell injury. The possibility that a CCl4-dependent disturbance of intrahepatocellular calcium homeostasis might be a linking mechanism was investigated with isolated hepatocytes in suspension. CCl4-dependent inhibition of very low density lipoprotein secretion was studied. On the basis of kinetic data, dose-response data, and failure of elevated cytosolic calcium levels to inhibit lipid secretion, it was concluded that disturbed intracellular calcium homeostasis probably is not important in CCl4-dependent inhibition of secretion of very low density lipoproteins.

Topics: Animals; Aspartate Aminotransferases; Calcimycin; Calcium; Carbon Radioisotopes; Carbon Tetrachloride; Digitonin; Fatty Liver; Homeostasis; In Vitro Techniques; Lipoproteins, VLDL; Male; Microsomes, Liver; Rats; Rats, Inbred Strains

Livers from 90 rabbits used in a factorial experiment relating cholesterol contents of various tissues to their serum cholesterol levels and duration of exposure were observed under light microscope. Livers from eight additional rabbits fed a 2% cholesterol diet for various periods up to 90 days were fixed in an aldehyde fixative containing 0.2% digitonin and observed under electron microscope. Digitonin-induced laminar and microtubular structures appeared five hours after cholesterol feeding. Fat vacuoles in both hepatocytes and Kupffer cells were first noted on the third day and increased in number and size to the 60th day but decreased on the 90th day. Adaptation of the liver to such excessive fat accumulation was evidenced by the gradual decrease of fat vacuoles and increase of binucleated cells.

Topics: Animals; Cholesterol; Cytoplasm; Digitonin; Fatty Liver; Kupffer Cells; Liver; Male; Microscopy, Electron; Microtubules; Rats; Vacuoles