Effects of glycyrrhizin on renal functions in association with the regulation of water channels.

It is well-known that the mineralocorticoid action of glycyrrhizin, which is the major component of Glycyrrhiza uralensis, is caused by a defect in the conversion of cortisol to cortisone by the inhibition of 11-beta-hydroxysteroid dehydrogenase enzyme activity. In the present study, we investigated the mechanisms of salt and water retention in the kidney of rats administered excess amounts of glycyrrhizin (200 mg/kg/day, p.o.). Up-regulation of aquaporin (AQP) 2 and 3 water channels was detected in the renal inner and outer medulla by Western blot analysis in rats treated with glycyrrhizin for 0.5, 1 and 2 consecutive weeks. Our results show that urine flow rates and sodium excretion rates in glycyrrhizin-treated rats were decreased significantly, but creatinine clearance (Ccr) was not altered. The decreases of urine volume and urinary sodium excretion in glycyrrhizin-treated rats were reversed by a 2-week injection of spironolactone, which is a well-known mineralocorticoid receptor (MR) blocker. These results suggest that the retention of water and salt in glycyrrhizin-treated rats is, at least in part, accounted for by the increased expression of AQP 2 and 3 in the kidney, which may be causally related to the MR.