benzofurans and Ureteral-Obstruction

Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.. To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.. Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.. SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both. SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.

Topics: Animals; Benzofurans; Depsides; Enhancer of Zeste Homolog 2 Protein; Fibrosis; Histones; Kidney; Kidney Diseases; Male; Mice; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Transforming Growth Factor beta1; Ureteral Obstruction

Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix. To study Twist1 functions in different macrophage subsets during kidney scar formation, we used two conditional mutant mouse models in which. Twist1 in infiltrating inflammatory macrophages but not in resident macrophages limited kidney fibrosis after ureteral obstruction by driving extracellular matrix degradation. Moreover, deletion of Twist1 in infiltrating macrophages attenuated the expression of MMP13 in CD11b. Twist1 in infiltrating myeloid cells mitigates interstitial matrix accumulation in the injured kidney by promoting MMP13 production, which drives extracellular matrix degradation. These data highlight the complex cell-specific actions of Twist1 in the pathogenesis of kidney fibrosis.

Topics: Actins; Animals; Benzofurans; Collagen Type I; CX3C Chemokine Receptor 1; Disease Models, Animal; Extracellular Matrix; Fibrosis; Gene Expression; Hydroxyproline; Kidney; Kidney Diseases; Macrophages; Macrophages, Peritoneal; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; Mice; Morpholines; Myeloid Cells; Twist-Related Protein 1; Ureteral Obstruction

To investigate the effect and mechanism of salvianolic acid B (SA-B) on renal interstitial fibrosis in rats induced by unilateral ureteral obstruction (UUO).. 18 male SD rats were randomly divided into 3 groups, 6 in each group. After the models were established, the rats were treated with SA-B for 2 weeks. Then their renal pathology were examined by hight microscope and electron microscopy Protein expression levels of alpha-smooth muscle actin (alpha-SMA) and E-cadherin (E-cad) in the obstructed kidney were analyzed by Western blot and Biochemistry assay.. Pathological examination of the kidney in model group showed tubules lumen widened and many inflammatory cells infiltrated, a part of renal tubule expanded and part of them atrophied. The tubular epithelial cells were karyorrhexis or karyolysis, some tubulars were atrophy. The protein expression of alpha-SMA were significantly up-regulated (P < 0.01) and E-cad were significantly down-regulated (P < 0.01) in the model group. After intervention with SA-B, the renal pathological status in the treatment group was significantly improved, the expression of alpha-SMA were significantly down-regulated (P < 0.05), but E-cad only a little up-regulated (P > 0.05).. SA-B could antagonize renal interstitial fibrosis mainly by maintaining epithelial phenotype, inhibiting the protein of alpha-SMA which is the principal effect cells that are responsible for the progressive kidney fibrosis.

Topics: Actins; Animals; Benzofurans; Blotting, Western; Cadherins; Disease Models, Animal; Fibrosis; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Tubules; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Ureteral Obstruction

The temporal relationship between changes in cytosolic free calcium and proximal tubular function was examined in rats following 24 h of unilateral and bilateral ureteral obstruction. Immediately after release of unilateral ureteral obstruction, proximal tubular functions were found to be normal. Cytosolic free calcium in isolated proximal tubules of the ureteral obstructed and contralateral kidneys were 160 +/- 8 and 172 +/- 15 nM, respectively. On the 7th day after release, cytosolic free calcium was not different from the sham control value (135 +/- 6 vs. 149 +/- 7 nM). In contrast, immediately after release of bilateral ureteral obstruction, cytosolic free calcium was increased significantly to 219 +/- 6 from 139 +/- 9 nM in sham-operated controls. Subsequent declines in cytosolic free calcium to 196 +/- 15 and 148 +/- 7 nM were observed at 3 and 7 days after release of bilateral ureteral obstruction, respectively. Over this period, renal tubular functions gradually returned to normal. Changes in cytosolic free calcium correlate well with the reported improvement in renal tubular function after release of bilateral ureteral obstruction. Therefore, one possible mechanism for the impairment of tubular function observed in bilateral ureteral obstruction may be an increase in cytosolic free calcium.

Topics: Animals; Benzofurans; Calcium; Fura-2; Kidney Tubules, Proximal; Male; Rats; Rats, Inbred Strains; Time Factors; Ureteral Obstruction

Unilateral ureteral obstruction (UUO) results in increased renal resistance as well as in exaggerated prostaglandin (PG) release from the obstructed hydronephrotic kidney (HNK). We have reported previously that platelet-activating factor (PAF) dose-dependently stimulates the release of PGs from both the HNK and unobstructed contralateral kidney (CLK), with CLK release being 10% that of the HNK. In the present report, we studied the interaction of PAF with its receptor by examining the effects of PAF-receptor antagonists on the release of PGs from the isolated perfused rabbit HNK and CLK stimulated by PAF; angiotensin II (AII), and bradykinin (BK) were also used as agonists. In the HNK, kadsurenone (3 microM) inhibited PAF-stimulated PGE2 and thromboxane B2 (TxB2) release by 28.2 and 62.5% respectively. CV-3988 (20 microM) and triazolam (5 microM) also preferentially diminished PAF-stimulated TxB2 release. In addition, all three drugs significantly diminished BK- and AII-stimulated TxB2 release, while CV-3988 was the only antagonist to affect peptide-stimulated PGE2 release. While effective against agonist-stimulated PG synthesis, these drugs had no direct effect on arachidonic acid metabolism to PGs. Furthermore, in the CLK, CV-3988 had no effect on BK- or AII-stimulated PGE2 release, whereas it totally inhibited PAF-stimulated release of PGE2. These results show that PAF-receptor antagonists in the HNK preferentially inhibit TxB2 release whether stimulated by PAF, AII or BK; in the CLK only PAF-stimulated PG release is affected. This biochemical difference may be of physiological significance and explain some of the functional differences between the HNK and CLK. Therefore, PAF may be an important mediator of some of the biochemical and functional changes associated with UUO.

Topics: Angiotensin II; Animals; Benzofurans; Dinoprostone; Kidney; Lignans; Male; Peptides; Platelet Activating Factor; Platelet Membrane Glycoproteins; Prostaglandins; Prostaglandins E; Rabbits; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Thromboxane B2; Triazolam; Ureteral Obstruction