Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase.
OBJECTIVE
To investigate the effects of aqueous extract of Astragali Radix (ARE) on the oxidative stress status and endothelial nitric oxide synthase level in adriamycin (ADR) nephropathy rats.


METHODS
ADR nephropathy rats were randomly treated with ARE (2.5 g/kg/d, n=6, ARE group), or benazepril (10mg/kg/d, n=6, angiotensin-converting enzyme inhibitor (ACEI) group) for ten weeks. Serum urea nitrogen, creatinine, albumin, total protein, cholesterol and 24-h urinary protein concentration were determined. Renal cortex catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) activities, and 24-h urinary NO(3)(-)/NO(2)(-) excretion were determined by chromatometry. Renal cortex cyclic guanosine monophosphate (cGMP) level was measured by enzyme immunoassay and eNOS expression was determined by immunohistochemistry.


RESULTS
ARE and ACEI treatments could remarkably reduce more 24h urinary protein excretion than that in ADR group (88.32±9.96 mg, 81.78±16.28 mg vs. 153.91±28.63 mg, P<0.01), and there was no difference between ARE and ACEI group. Renal cortex CAT, GSH-Px activities in ARE and ACEI group were significantly higher than ADR group, and renal cortex SOD activity in ARE group was higher than ADR group. Renal cortex MDA activity, cGMP level, and glomerular and tubular eNOS expression in ARE and ACEI group were lower than that in ADR group, and 24-h urinary NO(3)(-)/NO(2)(-) excretion in ARE group was lower than ADR group. Renal cortex MDA content (r=0.895, P<0.01), cGMP content (r=0.666, P<0.01) and eNOS expression in glomerulus (r=0.910, P<0.01) were strongly positively associated with 24h urinary protein excretion. And renal cortex SOD content was negatively associated with 24h urinary protein excretion (r=-0.861, P<0.01).


CONCLUSIONS
ARE may ameliorate the proteinuria by suppressing the over expression of eNOS, and inhibiting the oxidative injury in ADR nephropathy rats.
Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai 200040, China. youhz@sina.com
Huaizhou
H
You
Ye
Y
Lu
Dingkun
D
Gui
Ai
A
Peng
Jing
J
Chen
Yong
Y
Gu
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D027883:Astragalus Plant / Q000737:chemistry*; D004317:Doxorubicin / Q000633:toxicity*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D010936:Plant Extracts; D014867:Water; D004317:Doxorubicin; D052250:Nitric Oxide Synthase Type III