Delayed treatment with lithospermate B attenuates experimental diabetic renal injury

Geun Taek Lee, Hunjoo Ha, Mankil Jung, Hari Li, Soon Won Hong, Bong Soo Cha, Hyun Chul Lee, Young Dong Cho

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Extracellular matrix (ECM) accumulation in the glomerular mesangium is a characteristic feature of diabetic nephropathy. While transforming growth factor-β1 (TGF-β1) 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-β1, fibronectin, and collagen in STZR without significantly affecting plasma glucose. Both 30 mM of glucose and 100 uM of H2O2 significantly increased TGF-β1 and fibronectin protein secretion by mesangial cells. LAB at 10 μg/ml inhibited high glucose- and H2O2-induced TGF-β1 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-β1 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.

Original languageEnglish
Pages (from-to)709-720
Number of pages12
JournalJournal of the American Society of Nephrology
Volume14
Issue number3
DOIs
StatePublished - 1 Mar 2003

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