ABSTRACT
Objective To explore the roles of reactive oxygen species(ROS) and TGF-?1 in aldosterone-induced PAI-1 production.Methods Quiescent rat mesangial cells (MCs) were treated by aldosterone.The level of ROS in MCs induced by aldosterone was measured by confecal laser scanning microscopy and the TGF-?1 activity in the supematant of culture was measured by mink lung epithelial cell (Mvllu) proliferation inhibition MTT assay.Then,before the addition of aldosterone,MCs were pretreated with NAC or TGF-?1 neutralizing antibody to decrease cellular ROS or inhibit activity of TGF-?1 induced by aldosterone respectively.PAI-1 mRNA was examined by semi-quantification RT-PCR and PAI-1 protein by Western blotting.Results The intracellular ROS induced by aldosterone increased by 5-fold compared to that of control group,and the activity of TGF-?1 stimulated by aldosterone increased markedly.TGF-?1 neutralizing antibody and NAC effectively decreased aldosterone-induced PAI-1 mRNA expression by 30% and 32%,and PAI-1 protein expression by 21% and 11%,respectively.However,neither TGF-?1 neutralizing antibody nor NAC alone could regulate aldosterone-induced PAI-1 mRNA and protein expression to normal level in 24 hours.Conclusions ROS and TGF-?1 play important roles in up-regulation of aldosterone- induced PAI-1 in MCs.ROS and TGF-?1 are not the exclusive pathway of PAI-1 expression induced by aldosterone in MCs.
ABSTRACT
<p><b>BACKGROUND</b>Contrast media administration can result in severe nephrotoxicity under pathological conditions such as diabetic nephropathy, congestive heart failure, dehydration, et al. The purpose of this study was to evaluate the effects of dietary hypercholesterolemia on contrast media-induced changes in renal function, blood flow, and histopathology.</p><p><b>METHODS</b>Rats were fed either on a normal rodent diet (group N) or a high-cholesterol supplemented diet (group H; 4% cholesterol and 1% cholic acid) for 8 weeks. Half of the animals (n = 6) from each diet group were then given a tail vein injection of 60% diatrizoate (6 ml/kg; group NC and group HC) and the other half were administered saline. Total serum cholesterol, triglyceride, serum creatinine, creatinine clearance rate, fractional excretion of sodium and potassium, and cortical nitric oxide production were determined one day following contrast media administration. Renal blood flow was determined by color Doppler flow imaging and pulsed-mode Doppler. Renal histopathology was observed by light microscopy.</p><p><b>RESULTS</b>Total serum cholesterol and resistance indices of renal blood vessels increased significantly, while creatinine clearance rate and production of nitric oxide in the renal cortex decreased markedly in group HC and group H when compared to group N and group NC. The creatinine clearance rate decreased significantly in group HC compared to group H. Serum creatinine levels and fractional excretion of sodium and potassium in group HC were significantly higher than those in the other three groups. Severe tubular degeneration and necrosis, protein cast accumulation, and medullary congestion were found in group HC.</p><p><b>CONCLUSION</b>Hypercholesterolemia is a risk factor for contrast media-induced nephropathy. Hypercholesterolemia aggravates contrast media-induced nephrotoxicity through the reduced production of nitric oxide.</p>
Subject(s)
Animals , Male , Rats , Cholesterol, Dietary , Toxicity , Contrast Media , Toxicity , Kidney Diseases , Lipids , Blood , Nitric Oxide , Rats, Wistar , Renal CirculationABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of Valeriana officinalis var latifolia(VOL) on expression of transforming growth factor beta 1 (TGF-beta 1) in hypercholesterolemic rats and study its possible mechanisms.</p><p><b>METHOD</b>Dietary-induced hypercholesterolemia was induced in male Wistar rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, renal function and Mesangial matrix index were assessed. Moreover, immunohistochemical stain for TGF-beta 1 and type IV collagen were performed.</p><p><b>RESULT</b>VOL could reduce the serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine. Light microscopy and immunohistochemical stain revealed that in the same time of lowing serum lipid, Mesangial matrix index was significantly reduced, accompanied by decreased expression of TGF-beta 1 and type IV collagen.</p><p><b>CONCLUSION</b>VOL has the protective effect on lipid-induced nephropathy, and the inhibition of TGF-beta 1 expression might be the mechanism of VOL on renal protection.</p>