Effects of Celecoxib and Nordihydroguaiaretic Acid on Puromycin Aminonucleoside-Induced Nephrosis in the Rat

The selective cyclooxygenase-2 (COX-2) and 5-lipoxygenase (LOX) inhibitors might inhibit prostaglandin synthesis and reduce proteinuria. The present study was designed to investigate the anti-proteinuric effects of nordihydroguaiaretic acid (NDGA) as compared with celecoxib in puromycin aminonucleoside (PAN) nephrosis rats. Fifty five male Sprague-Dawley rats were divided into 4 groups; A, normal control; B, PAN group; C, PAN+COX-2 inhibitor (celecoxib) group; and D, PAN+5-LOX inhibitor (NDGA) group. After induction of PAN nephrosis through repeated injections of PAN (7.5 and 15 mg/100 g body weight), rats were treated with celecoxib, NDGA, or vehicle for 2 weeks. Twenty four hour urine protein excretions were significantly lower in PAN+celecoxib and PAN+NDGA groups than in PAN group. Serum creatinine (SCr) concentrations and 24 hr urine creatinine clearances (CCr) were not significantly different in the four groups. Electron microscopy showed that podocyte morphology was changed after the induction of PAN nephrosis and was recovered after celecoxib or NDGA administration. Celecoxib significantly recovered the expressions of nephrin, CD2AP, COX-2, and TGF-beta. NDGA also recovered TGF-betaexpression, but did not alter the expressions of nephrin, CD2AP and COX-2. The present study suggested that celecoxib and NDGA might effectively reduce proteinuria in nephrotic syndrome without impairing renal function.

Impact of Cyclosporin on Podocyte ZO-1 Expression in Puromycin Aminonucleoside Nephrosis Rats

Puromycin aminonucleoside (PAN) -induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. To investigate whether proteinuria in the PAN model is associated with an alteration of zonula occludens-1 (ZO-1) expression within the glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1 expression in this model, eighteen Sprague Dawley (SD) rats were assigned into three groups. Twelve rats received a single intraperitoneal injection of PAN (15 mg/100 g). The other six rats received an equal volume of saline (normal control group; control). CsA solution was administered intraperitoneally once a day for 20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1 +/- 5.4 mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher in the PAN rats (1021.9 +/- 128.9 mg/day, p< 0.01), and the CsA treatment partly reversed the increase in proteinuria in the PAN rats (556.4 +/- 102.3 mg/day, p< 0.05). Glomerular ZO-1 protein expressions were significantly increased in the PAN rats as compared to the control group on day 20 (176%, p< 0.01). CsA treatment for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by 71.1% (p< 0.05). CsA treatment significantly diminished the glomerular ZO-1 expression in the PAN rats as assessed by immunohistochemistry. CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model. These findings suggest the potential role of the slit diaphragm associated proteins in the development of the nephrotic syndrome, and CsA decreased the proteinuria probably by a direct action on the expression of these proteins in podocytes. Further investigations are needed to clarify the role of slit diaphragm associated proteins in the development of PAN nephrosis.

Intoxicaçao experimental por gentamicina em caes / Experimental gentamicin toxicosis in dogs

A toxicose experimental por gentamicina foi estudada em 11 caes. Dez caes receberam 10mg/kg de gentamicina por via intramuscular, 3 vezes ao dia, durante 14 dias. Outro cao recebeu a mesma dose por 10 dias. Os caes foram submetidos a eutanásia e necropsiados no 11§, 15§-19§, 21§, 27§ e 37§ dias do experimento. Os principais sinais clínicos foram anorexia, apatia, poliúria, polidipsia, diarréia, vômito e oligúria. Os achados laboratoriais foram enzimúria, cilindrúria, azotemia e isostenúria. As lesoes macroscópicas eram restritas aos rins, que estavam acentuadamente pálidos, tumefeitos e macios. Dois caes desenvolveram edema perirrenal discreto. Ao exame histológico do rim, dez caes tinham necrose tóxica aguda restrita aos túbulos contorcidos proximais. Regeneraçao das células epiteliais desses túbulos foi observada nos rins de todos os caes, principalmente na cortical externa, variando de mínima a acentuada e associada à dilataçao acentuada da luz tubular. Aos 37 dias os rins apresentavam-se morfologicamente recuperados. Nao foram observadas lesoes glomerulares, nem lesoes extra-renais de uremia. Concluiu-se que a gentamicina, na dose e freqüência administradas, foi tóxica para todos os caes, causando necrose tubular renal aguda com subseqüentes graus variados de regeneraçao tubular.