Antiproteinuric Effect of Ciclosporin A in Adriamycin Nephropathy in Rats

Desassis, J.F.; Raats, C.J.I.; Bakker, Marinka A.H.; Born, J. van den; Berden, J.H.M.

doi:10.1159/000189558

Cited by 29 publications

(12 citation statements)

References 18 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The changes reflect many functional alterations such as a drop in glomerular filtration rate, glomerular capillary damage and tubulotoxicity. These characteristic features of DOX-induced nephropathy are similar to those previously reported by other investigators (Desassis et al 1997;Montilla et al 1997;Venkatesan et al 1997;Zima et al 1997).…”

Section: Discussionsupporting

confidence: 91%

Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy

Kanter

2009

J Mol Hist

View full text Add to dashboard Cite

The aim of this study was designed to investigate the possible beneficial effects of the thymoquinone (TQ) in streptozotocine (STZ)-induced diabetes in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with TQ); each group contain ten animals. B and C groups received STZ. Diabetes was induced in two groups by a single intra-peritoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in two experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting 2 days after STZ injection. Treatment of TQ reduced the glomerular size, thickening of capsular, glomerular and tubular basement membranes, increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. We conclude that TQ therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of TQ treatment may indicate its usefulness as a potential treatment in diabetic nephropathy.

show abstract

Section: Discussionsupporting

confidence: 91%

Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy

Kanter

2009

J Mol Hist

View full text Add to dashboard Cite

show abstract

“…The role of SRL in the development of proteinuria is completely unknown. First of all, one can speculate that the increase in proteinuria is related to haemodynamic changes and/or changes in glomerular permselectivity after relief of CsA exposure (50). The insidious increase in proteinuria in our patients however, is against this hypothesis.…”

Section: Discussionmentioning

confidence: 58%

Conversion from Cyclosporine to Sirolimus in Stable Renal Transplant Recipients

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Time Response Study-In a previous study (36), we compared different doses of ADR. We found that a dose of 5 mg/kg body weight (BW) Adriamycin® (Adriablastina; Farmitalia, Milan, Italy) was optimal to induce proteinuria.…”

Section: Experimental Designmentioning

confidence: 99%

Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

Raats

Bakker

Born

et al. 1997

Journal of Biological Chemistry

Self Cite

105

View full text Add to dashboard Cite

Heparan sulfate, the polysaccharide side chain of heparan sulfate proteoglycan, is important for the permselective properties of the glomerular basement membrane. In this report, we show a role for hydroxyl radicals in heparan sulfate degradation and an enhanced glomerular basement membrane permeability. First, in enzyme-linked immunosorbent assay, exposure of coated heparan sulfate (proteoglycan) to reactive oxygen species resulted in a ؎50% decrease of binding of a monoclonal antibody against heparan sulfate, whereas binding of an antibody against the core protein remained unaltered. Second, on polyacrylamide gel electrophoresis, the molecular weight of heparan sulfate exposed to radicals was reduced which indicates depolymerization. Both in enzyme-linked immunosorbent assay and gel electrophoresis, hydroxyl radicals are instrumental for heparan sulfate degradation as shown by the addition of various radical scavengers. Third, in an experimental model for human nephrotic syndrome (Adriamycin nephropathy in rats), glomerular basement membrane staining of two recently described anti-heparan sulfate antibodies (JM403 and KJ865) was reduced by 24 and 43%. Treatment of Adriamycin-exposed rats with the hydroxyl radical scavenger dimethylthiourea both reduced albuminuria by 37% (p < 0.01) and partly prevented loss of heparan sulfate staining by 53% (JM403) and 39% (KJ865) (p < 0.03). In contrast to the heparan sulfate side chains, the core protein expression and the extent of glycanation did not change in Adriamycin nephropathy. We conclude that glomerular basement membrane heparan sulfate is susceptible to depolymerization by hydroxyl radicals leading to loss of glomerular basement membrane integrity and albuminuria.Heparan sulfate (HS) 1 is the anionic polysaccharide side chain of heparan sulfate proteoglycan (HSPG) present in basement membranes, extracellular matrix, and on the cell surface of many (if not all) cell types (1-3). Several investigators have shown that HS plays an important role in the permselective properties of the glomerular basement membrane (GBM) (4, 5). Enzymatic digestion of HS by heparitinase resulted in an increased passage of native ferritin and albumin through the GBM (6, 7). Furthermore, intravenous injection of a monoclonal antibody (mAb) directed against HS induces acute, selective proteinuria in rats (8). A reduction in GBM HS-associated anionic sites was found with cationic probes in several human and experimental proteinuric glomerulopathies (9, 10). With recently developed antibodies directed against GBM HSPG core protein and the HS side chain (11, 12), we demonstrated a decrease in HS staining in the GBM in different human proteinuric glomerulopathies, whereas the staining of the HSPG core protein remained unaltered (13). The mechanism responsible for this observation remains to be elucidated. In lupus nephritis, masking of HS by autoantibodies complexed to nucleosomes is proposed as a mechanism for the decrease in HS staining and albuminuria (14). In human and experimental diabe...

show abstract

Antiproteinuric Effect of Ciclosporin A in Adriamycin Nephropathy in Rats

Cited by 29 publications

References 18 publications

Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy

Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy

Conversion from Cyclosporine to Sirolimus in Stable Renal Transplant Recipients

Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

Contact Info

Product

Resources

About