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Delayed treatment with lithospermate B attenuates experimental diabetic renal injury

Authors
 GEUN TAEK Lee  ;  Hunjoo Ha  ;  Young Dong Cho  ;  Hyun Chul Lee  ;  Bong Soo Cha  ;  Soon Won Hong  ;  Hari Li  ;  Mankil Jung 
Citation
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.14(3) : 709-720, 2003 
Journal Title
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 
ISSN
 1046-6673 
Issue Date
2003
MeSH
Albuminuria/drug therapy ; Albuminuria/metabolism ; Albuminuria/pathology ; Animals ; Blood Glucose/metabolism ; Cells, Cultured ; Diabetes Mellitus, Experimental/drug therapy* ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Drugs, Chinese Herbal/chemistry ; Drugs, Chinese Herbal/pharmacology* ; Fibronectins/metabolism ; Free Radical Scavengers/chemistry ; Free Radical Scavengers/pharmacology* ; Glomerular Mesangium/metabolism ; Glomerular Mesangium/pathology ; Glucose/pharmacology ; Hydrogen Peroxide/pharmacology ; Male ; Oxidants/pharmacology ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1
Keywords
12595507
Abstract
Extracellular matrix (ECM) accumulation in the glomerular mesangium is a characteristic feature of diabetic nephropathy. While transforming growth factor-beta1 (TGF-beta1) is the final mediator of ECM accumulation, reactive oxygen species (ROS) and protein kinase C (PKC) are the upstream signaling molecules that mediate hyperglycemia-induced ECM expansion. Magnesium lithospermate B (LAB) is an active component isolated from Salvia miltiorrhizae with known renoprotective properties due to its antioxidative effects. Thus, the present study examined the effects of LAB on renal injury in streptozotocin-induced diabetic rats (STZR) and on the activation of mesangial cells cultured under high glucose conditions. Ten micrtograms of LAB/kg per day was started 8 wk after streptozotocin injection and continued for a period of 8 wk. It significantly suppressed renal malondialdehyde (MDA), microalbuminuria, glomerular hypertrophy, mesangial expansion, and the upregulation of renal TGF-beta1, fibronectin, and collagen in STZR without significantly affecting plasma glucose. Both 30 mM of glucose and 100 uM of H(2)O(2) significantly increased TGF-beta1 and fibronectin protein secretion by mesangial cells. LAB at 10 micro g/ml inhibited high glucose- and H(2)O(2)-induced TGF-beta1 and fibronectin secretion. LAB also inhibited glucose-induced intracellular ROS generation and PKC activation in mesangial cells, but it did not directly inhibit PKC activity at dosages that inhibited ROS generation. The in vitro data of this study show that LAB inhibits ROS generation leading to PKC activation and TGF-beta1 and fibronectin upregulation in mesangial cells cultured under high glucose conditions. Moreover, delayed treatment with LAB was found to significantly suppress the progression of renal injury in STZR. LAB may become a new therapeutic agent for the treatment of diabetic nephropathy.
Files in This Item:
T200301117.pdf Download
DOI
OAK-2003-00049
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Hyun Chul(이현철)
Lee, Hye Ree(이혜리)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113209
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