Electrolyte Blood Press.  2011 Dec;9(2):55-62. 10.5049/EBP.2011.9.2.55.

Effects of Dietary Salt Restriction on Puromycin Aminonucleoside Nephrosis: Preliminary Data

• Jo CH
• Kim S
• Park JS
• Kim GH

• KMID: 2168385
• DOI: http://doi.org/10.5049/EBP.2011.9.2.55

Abstract

Proteinuria is a major promoter that induces tubulointerstitial injury in glomerulopathy. Dietary salt restriction may reduce proteinuria, although the mechanism is not clear. We investigated the effects of dietary salt restriction on rat kidneys in an animal model of glomerular proteinuria. Male Sprague-Dawley rats were used and divided into 3 groups: vehicle-treated normal-salt controls, puromycin aminonucleoside (PA)-treated normal-salt rats, and PA-treated low-salt rats. PA was given at a dose of 150 mg/kg BW at time 0, followed by 50 mg/kg BW on days 28, 35, and 42. Sodium-deficient rodent diet with and without additional NaCl (0.5%) were provided for normal-salt rats and low-salt rats, respectively. On day 63, kidneys were harvested for histopathologic examination and immunohistochemistry. PA treatment produced overt proteinuria and renal damage. Dietary salt restriction insignificantly reduced proteinuria in PA-treated rats, and PA-treated low-salt rats had lower urine output and lower creatinine clearance than vehicle-treated normal-salt controls. When tubulointerstitial injury was semiquantitatively evaluated, it had a positive correlation with proteinuria. The tubulointerstitial injury score was significantly increased by PA treatment and relieved by low-salt diet. ED1-positive infiltrating cells and immunostaining for interstitial collagen III were significantly increased by PA treatment. These changes appeared to be less common in PA-treated low-salt rats, although the differences in PA-treated normal-salt versus low-salt rats did not reach statistical significance. Our results suggest that renal histopathology in PA nephrosis may potentially be improved by dietary salt restriction. Non-hemodynamic mechanisms induced by low-sodium diet might contribute to renoprotection.

Keyword

puromycin; diet, sodium-restricted; proteinuria; kidney

MeSH Terms

Animals
Collagen
Creatinine
Diet
Diet, Sodium-Restricted
Humans
Immunohistochemistry
Kidney
Male
Models, Animal
Nephrosis
Proteinuria
Puromycin
Puromycin Aminonucleoside
Rats
Rats, Sprague-Dawley
Rodentia
Collagen
Creatinine
Puromycin
Puromycin Aminonucleoside

Figure

• 

  Fig. 1 Histopathology of the Kidney Using Periodic AcidSchiff (PAS) Staining. Representative sections are shown from each group (A), and results of semiquantitative evaluation of tubulointerstitial injury are summarized in a bar graph (B). Magnification ×200. PA, puromycin aminonucleoside; NS, normalsalt diet; LS, lowsalt diet.*P < 0.05 versus VehicleNS.†P < 0.05 versus PANS.

• 

  Fig. 2 Correlation between Proteinuria and Tubulointerstitial Injury Score. Tubulointerstitial injury correlates positively with proteinuria in this animal experiment.

• 

  Fig. 3 Immunohistochemistry for ED1 in Rat Kidneys. Representative sections are shown from each group (A), and results of quantitative evaluation of immunostaining are summarized in a bar graph (B). Magnification ×200. PA, puromycin aminonucleoside; NS, normalsalt diet; LS, lowsalt diet.*P < 0.05 versus VehicleNS.

• 

  Fig. 4 Immunohistochemistry for Osteopontin in Rat Kidneys. Representative sections are shown from each group (A), and results of quantitative evaluation of immunostaining are summarized in a bar graph (B). No significant differences were noted between groups. Magnification ×200. PA, puromycin aminonucleoside; NS, normalsalt diet; LS, lowsalt diet.

• 

  Fig. 5 Immunohistochemistry for Collagen III in Rat Kidneys. Representative sections are shown from each group (A), and results of quantitative evaluation of immunostaining are summarized in a bar graph (B). Magnification ×200. PA, puromycin aminonucleoside; NS, normalsalt diet; LS, lowsalt diet.*P < 0.05 versus VehicleNS.

• 

  Fig. 6 Histopathology of the Kidney Using Masson's Trichrome Staining. Representative sections are shown from each group (A), and bluetored pixel ratios are expressed in a bar graph (B). No significant differences were noted between groups. Magnification ×200. PA, puromycin aminonucleoside; NS, normalsalt diet; LS, lowsalt diet.

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