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.

Acute glomerulonephritis is characterized by the presence of neutrophils within glomeruli and the generation of reactive oxygen species (ROS) by activated polymorphonuclear leukocytes (PMNs). Hydrogen peroxide (H2O2) and other ROS including hypothalous acids have been implicated in PMN mediated injury. To determine the role of specific ROS in PMN mediated glomerular injury, isolated rat glomeruli were incubated for 30 minutes at 37 degrees C with H2O2, with H2O2 and myeloperoxidase, or with activated PMNs. Scavengers of ROS were included in some experiments. PMNs were harvested from rat peritoneal cavity and activated with phorbol myristate acetate (PMA). Glomerular albumin permeability (Palbumin) was calculated from the volume response to an oncotic gradient. Palbumin of glomeruli incubated with H2O2 (10(-3) or 10(-1) M) was not increased, while Palbumin after incubation with H2O2 and MPO was markedly increased (0.94 +/- 0.004). Palbumin after incubation with PMA, or with non-activated PMNs was not different from that of control glomeruli, Palbumin of the glomeruli incubated with activated PMNs increased (0.85 +/- 0.01, P< 0.001). This increase in Palbumin was inhibited by superoxide dismutase, catalase, or taurine (Palbumin = 0.035 +/- 0.06, -0.39 +/- 0.10, 0.028 +/- 0.06, respectively) and ameliorated by sodium azide (Palbumin = 0.21 +/- 0.03). In contrast, dimethyl sulfoxide did not prevent the increase in Palbumin (Palbumin = 0.92 +/- 0.01). Our results show that the hypohalous acid derived from that of H2O2-MPO-halide system is capable of increasing Palbumin. We conclude that hypohalous acid may be the primary mediator of the immediate increase in glomerular protein permeability induced by PMNs.

It has been well demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) can retard the progression of renal failure and kidney sclerosis in patients and animal models with glomerular diseases. The aim of this study was to observe the influences of ACEI on intrarenal Ang II and TGFi81 local formation and their relation to renal protective effects. Experimental glomerulosclerosis with nephrotic syndrome was induced in unilateral nephrectomized rats with repeated injections of adriamycin. Rats were randomly divided into three groups: 1) a sham-operated control group (n = 8); 2) an NS group treated with ACE! (benazepril 4 mg/kg/d) (n =10), and 3) an NS group not treated (n =10). After 8 wk, serum, urine and renal tissue were collected for study. ACE activity and Ang II concentration in renal tissue were measured by colorimetry and radioimmunoassay, respectively. Immunohistochemistry staining was employed for transforming growth factor-,81 (TGF/91) and extracellular matrix (ECM) examination. .01 in all cases). In the ACEI treated group, these histologic benefits coincided with a reduced expression of TGFi91 in both tubular cells and sclerosed glomeruli in protein as well as mRNA level. These findings provide further evidence that ACE! (benazepril) can prevent the progression of renal damage in both the function and morphologic changes which associated with a down-regulation of intrarenal Ang II level through the relative inhibition of renal ACE activity. The blocking of the Intrarenal renin angiotensin system (RAS) might contribute to the inhibition of TGFj91 local formation and the TGFi91-mediated ECM accumulation that are related to the renal protective effects of ACE!. (Hypertens Res 1999; 22: 223-228)

Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (L_p) and capillary albumin permeability (P_albumin)· Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10^-9,10^-7 and 10^-5M) for up to 5 h at 37⁰C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. L_p was calculated from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. P_albumin was calculated from a change in relative volume of glomeruli in response to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+0.9, 7.9 ± 1.0 and 10.0+1.0%, respectively, with PAF 10^-9,10^-7 and 10^-5M). Incubation of glomeruli with PAF 10^-7M for 60 min at 37°C caused a significant decrease in L_p (2.25 ± 0.30 vs. control 3.12 ± 0.28 µl·min^-1 •mm Hg^-1 cm^-1, n= 5). P_albumin of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10^-5M) after 3 h of incubation (0.60 ± 0.18, n = 15, vs. control 0.00 ± 0.08, n = 20), whereas lower concentrations of PAF (10^-7 or 10^-9M) required at least 5 h of incubation with glomeruli to cause a significant increase in P_albumin (0.45 ± 0.09 and 0.48 ± 0.07, respectively, n = 15, vs. control 0.00 ± 0.08, n = 15). We conclude that PAF has multiple direct effects on glomerular functions, which are time dependent and may contribute to the altered capillary permeability in vivo.