Renoprotective effect of breviscapine through suppression of renal macrophage recruitment in streptozotocin-induced diabetic rats.
OBJECTIVE
Experimental and clinical evidence has consistently demonstrated that renal macrophage infiltration is one of the most important events for the progression of diabetic nephropathy. Breviscapine is a flavonoid extracted from the Chinese herb Erigeron breviscapus. Previously, it was shown that treatment with breviscapine attenuated renal injury in the diabetic rats. The purpose of this study is to investigate whether the renoprotective effect of breviscapine is through suppression of renal macrophage recruitment in diabetic rats.


METHODS
Diabetes was induced bystreptozotocin injection, and breviscapine was administered orally at a dose of 20 mg/kg/day for 8 weeks. Control rats received vehicle or breviscapine with the same schedule.


RESULTS
Breviscapine treatment markedly inhibited both an increase of albuminuria and glomeruli hypertrophy and tubulointerstitial injury without modifying mean arterial blood pressure and creatinine clearance. Levels of malondialdehyde and protein kinase C activities were markedly higher and antioxidant enzyme activities such as superoxide dismutase, catalase as well as glutathione peroxidase were significantly lower in the kidneys of diabetic rats than of the control group, breviscapine administration markedly remitted these changes. ED-1-positive cells and expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in glomeruli and tubulointerstitium were all markedly elevated but were significantly reduced by breviscapine. Western blot analysis noted that the expression of transforming growth factor beta1 protein was increased 1.8-fold in the kidney in diabetic rats, breviscapine treatment could reduce increased expression of TGF-beta1 protein by 47%.


CONCLUSIONS
This study describes a novel mechanism by which breviscapine confers a renoprotective effect.
Qi
Xiang Ming
XM
Department of Nephropathy, The First Affiliated Hospital of AnHui Medical University, Hefei, PR China.
Wu
Guo Zhong
GZ
Wu
Yong Gui
YG
Lin
Hui
H
Shen
Ji Jia
JJ
Lin
Shan Yan
SY
D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D005419:Flavonoids / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
D018932:Chemokine CCL2; D005419:Flavonoids; C061097:breviscapine; D018799:Intercellular Adhesion Molecule-1