Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis

Abstract

The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.

Amelioration of Antioxidant Enzyme Suppression and Proteinuria in Cyclosporin-Treated Puromycin Nephrosis

“…How ever, the PAN and CS-induced serum creatinine elevation in their study was not observed in our study. Since the morphologic features of the PAN model vary acording to the magnitude of the initial injury and whether ongoing injury is occurring [26], the study of Kokui et al [6] may have more severe initial glomerular injury induced by PAN, and further reduction of GFR caused by CS may lead to results different from ours.…”

“…However, there are conflicting data as Kokui et al [6] have found no difference in anionic sites between PAN rats and CS-treated PAN rats. A fall in glomerular filtration rate (GFR) cause by CS is suggested to be responsible for the reduction of proteinuria [6], CS-induced amelioration of glomerular injury observed in the present study was in contrast to the study of Kokui et al [6], who have found no difference of glomerular mor phology between PAN rats and CS-treated PAN rats. How ever, the PAN and CS-induced serum creatinine elevation in their study was not observed in our study.…”

“…Although clinical data indicate the reduction of protein uria by CS in minimal-change nephrotic syndrome and nephrotic syndrome associated with FSGS [1][2][3][4], there has been little published information about the effect of CS on proteinuria in PAN nephrosis [5,6,22], Shibasaki et al [5] and Kokui et al [6] have observed reduction of proteinuria induced by CS in PAN rats. Thaiss et al [22] have contrarily not found such reduction.…”

“…Several studies suggest that cyclosporin (CS) may have a beneficial effect in reducing proteinuria in minimal-change nephrotic syndrome and nephrotic syndrome associated with focal segmental glomerulosclerosis (FSGS) [1][2][3][4], Re cently, animal investigations have demonstrated that CS reduces proteinuria in rats with puromycin aminonucleo side (PAN) nephrosis [5][6] which has been regarded as a model of minimal-change nephrotic syndrome and FSGS [7], However, the mechanism responsible for the CS-induced reduction of proteinuria is not clear. It has been demonstrated that the proteinuria and glomerular injuries in PAN nephrosis are related to reactive oxygen species (ROS) and are protected by either exogenous [8][9][10] or glucocorticoid-induced intrinsic antioxidant enzymes [11], Reduced glutathione (GSH) also plays a role in PAN-in duced proteinuria [12].…”

Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators and proteoglycans in experimental nephrosis

“…CsA is an immunosuppressive drug that is efficient in the treatment of experimental and human nephrosis [7]. However, the mechanisms by which CsA reduces proteinuria in both situations are unknown.…”