Journal List > Korean J Physiol Pharmacol > v.12(6) > 1025572

Bae, Lee, Park, Bae, Ma, Kim, and Kim: Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

Abstract

The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+ -ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT.

REFERENCES

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Fig. 1.
Expression of Na+/K+-ATPase in cortex/OSOM. (A) The expression of Na+/K+-ATPase was significantly decreased in gentamicin-treated rats, while that of β-actin remained unaltered. Each column represents mean±SEM of 4 rats (∗p<0.05, compared with control). (B) Immunostaining of Na+/K+-ATPase showed decreased expression in gentamicintreated rats. Magnification ×400.
kjpp-12-331f1.tif
Fig. 2.
Expression of NHE3 in cortex/OSOM. (A) The protein expression of NHE3 was significantly decreased in gentamicin-treated rats. Each column represents mean±SEM of 4 rats (∗p <0.05, compared with control). (B) Immunostaining of NHE3 showed decreased expression in gentamicintreated rats. Magnification ×400.
kjpp-12-331f2.tif
Fig. 3.
Expression of NBC1 in cortex/OSOM. (A) The protein expression of NBC1 was significantly decreased in gentamicin-treated rats. Each column represents mean±SEM of 4 rats (∗p <0.05, compared with control). (B) Immunostaining of NBC1 showed decreased expression in gentamicintreated rats. Magnification ×400.
kjpp-12-331f3.tif
Fig. 4.
Expression of AQP1 in cortex/OSOM. (A) The protein expression of AQP1 was significantly decreased in gentamicin-treated rats. Each column represents mean±SEM of 4 rats (∗p <0.05, compared with control). (B) Immunostaining of AQP1 showed decreased expression in gentamicintreated rats. Magnification ×400.
kjpp-12-331f4.tif
Fig. 5.
Expression of OAT1 and OAT3 mRNA in whole kidney. Each column represents mean±SEM of 4 rats (∗p <0.05, compared with control).
kjpp-12-331f5.tif
Fig. 6.
Expression of OAT1 in cortex/OSOM. (A) The protein expression of OAT1 was significantly decreased in gentamicin-treated rats. Each column represents mean±SEM of 4 rats (∗p<0.05, compared with control). (B) Immunostaining of OAT1 showed decreased expression in gentamicintreated rats. Magnification ×400.
kjpp-12-331f6.tif
Table 1.
Urinary parameters in control and gentamicin-treated rats
  Control (n=4) Gentamicin (n=4)
Body weight (g) 245±5 235±5
UO (mL/day) 9.9±0.9 24.9±1.4
Pcr (mg/dL) 0.55±0.03 1.08±0.19
Ccr (mL/min) 0.91±0.09 0.47±0.07
PNa (mEq/L) 140.2±0.3 140.3±1.5
UNa×UO (mEq/day) 2.58±0.23 2.39±0.28
FENa (%) 1.4±0.1 2.7±0.5
Uosm (mosm/kgH2O) 1613±43 712±77
Posm (mosm/kgH2O) 299±2 308±3
U/P osm 5.4±0.2 2.3±0.3
TcH2O(μl/min/kg) 123±15 94±16

Values are expressed as mean±SEM. The values were measured onthe last day of experiment. UO, urine output; Pcr, plasma creatinine; Ccr, creatinine clearance; PNa, plasma sodium; UNa×UO, urinary sodium excretion; FENa, fractional excretion of sodium; Uosm, urine osmolality; Psom, plasma osmolality; U/P osm, urine to plasma osmolality ratio; TcH2O, solute-free water absorption.

p<0.05, compared with control.

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