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Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase

You, Huaizhou, Lu, Ye, Gui, Dingkun, Peng, Ai, Chen, Jing, Gu, Yong
Journal of ethnopharmacology 2011 v.134 no.1 pp. 176-182
albumins, catalase, cholesterol, cortex, creatinine, cyclic GMP, enzyme immunoassays, enzyme inhibitors, excretion, glutathione peroxidase, guanosine monophosphate, kidney diseases, malondialdehyde, nitric oxide synthase, oxidative stress, peptidyl-dipeptidase A, rats, superoxide dismutase, urea nitrogen
AIM OF THE STUDY: 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. MATERIALS AND METHODS: ADR nephropathy rats were randomly treated with ARE (2.5g/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 NO₃ ⁻/NO₂ ⁻ 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±9.96mg, 81.78±16.28mg vs. 153.91±28.63mg, 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 NO₃ ⁻/NO₂ ⁻ 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.