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 a 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 hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.
Rossi
T
T
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Italy. rossti-27@mail.unimo.it
Fano
R A
RA
Castelli
M
M
Malagoli
M
M
Ruberto
A I
AI
Baggio
G
G
Zennaro
R
R
Migaldi
M
M
Barbolini
G
G
D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006034:Glycyrrhetinic Acid / Q000633:toxicity*; D019695:Glycyrrhizic Acid / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors
D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid