Glycyrrhizic acid attenuated glycative stress in kidney of diabetic mice through enhancing glyoxalase pathway.

Antiglycative effects of glycyrrhizic acid (GA) in kidney of diabetic mice were examined. GA at 0.05, 0.1, and 0.2% was supplied to diabetic mice for 9 wk. Results showed that GA intake increased its deposit in kidney, raised plasma insulin level, decreased plasma glucose and blood urine nitrogen levels, and improved creatinine clearance rate (p < 0.05). GA intake dose-dependently reduced renal carboxymethyllysine level, and at 0.1 and 0.2% decreased plasma HbA1c, urinary glycated albumin, and renal pentosidine levels (p < 0.05). Dietary GA intake declined renal aldose reductase activity and protein expression, as well as lowered renal fructose and sorbitol levels (p < 0.05). GA intake dose-dependently increased glyoxalase-1 activity and expression, and decreased renal methylglyoxal level (p < 0.05). This compound at 0.1 and 0.2% raised glyoxalase-2 activity and protein expression, and increased d-lactate formation (p < 0.05). GA intake dose-dependently suppressed renal expression of nuclear factor kappa B (NF-κB) p65 and p-p38, decreased reactive oxygen species production, and retained glutathione content (p < 0.05). This compound at 0.1 and 0.2% downregulated renal expression of NF-κB p50 and p-ERK1/2 (p < 0.05), and lowered renal level of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). These findings suggest that glycyrrhizic acid is an antiglycative and renal-protective agent.