AMMONIUM GLYCYRRHIZINATE (AMGZ) EFFECTS ON MEMBRANE INTEGRITY

Potential mechanisms by which ammonium glycyrrhizinate (AMGZ) modifies biomembranes and promotes transcellular permeation of low molecular w eight markers were investigated. The effects of increasing AMGZ concen tration, pH, and ionic strength on erythrocyte hemolysis and on the st eady-state fluorescence anisotropy, r, of fluorophore-labeled tracheal and erythrocyte ghost membranes were studied. At AMGZ concentrations greater than 1%, significant hemolytic activity was observed. Hemolysi s was not observed over either the pH or the ionic strength ranges pro duced by corresponding concentrations of AMGZ. A significant decrease in r, a measure of lipid packing order, was observed in erythrocyte gh ost membranes at AMGZ concentrations greater than 0.5 and 1.0% AMGZ in both lipid-water interfaces labeled with trimethylammonio)phenyl]-6-p henyl-1,3,5-hexatriene (TMA-DPH) and core lipid domains labeled with 1 ,6-diphenyl-1,3,5-hexatriene (DPH), respectively. Fluorescence lifetim e studies indicated that the DPH and TMA-DPH probes were to some degre e sensitive to AMGZ and suggested the possibility of some contribution s of direct AMGZ: probe interaction to interpretation of the fluoresce nce studies. A significant decrease in lipid packing order was also ob served predominantly at the lipid-water interace of apical tracheal ce ll membranes at AMGZ concentrations greater than 0.5%. The lipid packi ng order for bovine trachea apical membranes and erythrocyte ghosts wa s not affected by varied pH or ionic strength produced by correspondin g AMGZ additions. Collectively, results suggested that direct effects of AMGZ, as opposed to accompanying pH or ionic strength changes, on p rimarily membrane components at the lipid-water interface may contribu te to alterations in membrane permeability to low molecular weight sub stances.