Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: An experimental in vivo study

The ingestion of large quantities of glycyrrhizin, whether as a drug or st sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokalia emia-induced arrythmias. Glycyrrhizin is also known to isomerize into the g lycyrrhetic (or glycyrrhetinic) acids 18 alpha- and 18 beta-. In previous w orks, we reported that these metabolites cause bouts of hypertension and re duction in diuresis at low doses in the rat. In particular, the alpha isome r causes significant elimination of the calcium ion in the urine. The prese nt findings confirm that 18 alpha-glycyrrhetic acid is more toxic than eith er glycyrrhizin or the beta isomer. Histopathological study of tissue sampl es taken from rats treated with the alpha isomer also reveal selective dama ge to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic trea tment, they manifest themselves in acute treatment and correlate closely wi th the electrocardiographic changes recorded in rats acutely treated with 1 8 alpha-glycyrrhetic acid.