title: Glycyrrhizic acid attenuated glycative stress in kidney of diabetic mice through enhancing glyoxalase pathway.
abstract: METHODS
  Antiglycative effects of glycyrrhizic acid (GA) in kidney of diabetic mice were examined.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These findings suggest that glycyrrhizic acid is an antiglycative and renal-protective agent.
authors.affiliation: Center of Aging Research, China Medical University Hospital, Taichung City, Taiwan.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Wen-hu
authors.initials: WH
authors.lastname: Liu
authors.forename: Mei-chin
authors.initials: MC
authors.lastname: Yin
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000652:urine; D005978:Glutathione / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D013012:Sorbitol / Q000652:urine; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D000449:Aldehyde Reductase; D018932:Chemokine CCL2; D005632:Fructose; D005978:Glutathione; D019695:Glycyrrhizic Acid; D018799:Intercellular Adhesion Molecule-1; D007064:L-Iditol 2-Dehydrogenase; D007791:Lactoylglutathione Lyase; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013012:Sorbitol; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C491768:Ccl2 protein, mouse; C090509:Icam1 protein, mouse
keywords: Diabetic nephropathy; Glycation; Glycyrrhizic acid; Glyoxalase-1; Methylglyoxal