Inhibitory effect of Tripterygium wilfordii multiglycoside on increased glomerular albumin permeability in vitro.
BACKGROUND
Tripterygium wilfordii Hook F is a medicinal plant used for the treatment of glomerulonephritis in China. We studied the effect of Tripterygium wilfordii multiglycoside (TWG) on glomerular albumin permeability (Palbumin) in vitro.


METHODS
Isolated rat glomeruli were incubated with protamine (600 micrograms/ml) for 30 min, or with human recombinant tumour necrosis factor (TNF-alpha 0.4 ng/ml), superoxide (10 units/ml), or serum from a focal segmental glomerular sclerosis (FSGS) patient for 10 min at 37 degrees C. TWG, 1 mg/ml, was added in parallel tubes to study the effect on Palbumin. Control glomeruli were incubated under identical conditions. The albumin reflection coefficient (sigma albumin) was calculated from the change in glomerular volume in response to an applied oncotic gradient. Convectional permeability (Palbumin) was calculated as (1 - sigma albumin).


RESULTS
Compared with controls, protamine increased the Palbumin of glomeruli (0.83 +/- 0.05, n = 25, vs 0.18 +/- 0.03, n = 20); pretreatment with TWG blocked this effect (0.13 +/- 0.04, n = 25). TNF-alpha also increased the Palbumin (0.79 +/- 0.04, n = 24 vs 0.04 +/- 0.07, n = 19); preincubation with TWG blocked this effect (0.03 +/- 0.09, n = 24). Palbumin of glomeruli incubated with xanthine and xanthine oxidase, resulting in the production of superoxide, also increased as compared to controls (0.85 +/- 0.04, n = 15 vs 0.08 +/- 0.05, n = 14); TWG blocked this effect as well (0.21 +/- 0.08, n = 14). FSGS serum also increased Palbumin of glomeruli significantly (0.88 +/- 0.02, n = 49 vs 0.00 +/- 0.02, n = 49); preincubation with TWG blocked this effect (0.05 +/- 0.07, n = 30). TWG by itself had no effect on Palbumin (0.19 +/- 0.10, n = 15).


CONCLUSIONS
Our results show that TWG blocks protamine, TNF-alpha, superoxide, and FSGS serum-mediated increase in glomerular albumin permeability in vitro. We conclude that reduction of proteinuria by Tripterygium wilfordii multiglycoside in various kinds of glomerular diseases in vivo might be due to protection of the glomerular filtration barrier.
Sharma
M
M
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Li
J Z
JZ
Sharma
R
R
Artero
M
M
Ge
X
X
McCarthy
E T
ET
Wang
H Y
HY
Savin
V
V
D000818:Animals; D001790:Blood Physiological Phenomena; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010539:Permeability / Q000187:drug effects; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology; D029757:Tripterygium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D006027:Glycosides; D011479:Protamines; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides