The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지

Decreased Expression of $Na^+/K^+$-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

  • Bae, Woo-Kyun (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Lee, Jong-Un (Department of Physiology, Chonnam National University Medical School) ;
  • Park, Jeong-Woo (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Bae, Eun-Hui (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Ma, Seong-Kwon (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Kim, Suhn-Hee (Department of Physiology, Chonbuk National University Medical School) ;
  • Kim, Soo-Wan (Department of Internal Medicine, Chonnam National University Medical School)
  • Published : 2008.12.31
Download PDF
⟨ Previous Next ⟩

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 ($200{\sim}250\;g$) 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.

Keywords

References

  1. Bae EH, Kim IJ, Oh YW, Bae WK, Park JW, Ma SK, Kim NH, Choi KC, Lee J, Kim SH, Kim SW. Increased expression of endothelin-1 and CYP11B2 in gentamicin-induced nephropathy in rat kidney. Korean J Nephrol 26: 660-668, 2007
  2. Bae EH, Lee KS, Lee J, Ma SK, Kim NH, Choi KC, Frokiaer J, Nielsen S, Kim SY, Kim SZ, Kim SH, Kim SW. Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats. Am J Physiol Renal Physiol 294: F272-280, 2008 https://doi.org/10.1152/ajprenal.00352.2007
  3. Baylis C, Rennke HR, Brenner BM. Mechanisms of the defect in glomerular ultrafiltration associated with gentamicin administration. Kidney Int 12: 344-353, 1977 https://doi.org/10.1038/ki.1977.121
  4. Bennett WM. Drug nephrotoxicity: an overview. Ren Fail 19: 221-224, 1997 https://doi.org/10.3109/08860229709026280
  5. Besarab A, Silva P, Epstein FH. Multiple pumps for sodium reabsorption by the perfused kidney. Kidney Int 10: 147-153, 1976 https://doi.org/10.1038/ki.1976.88
  6. Gainza FJ, Minguela JI, Lampreabe I. Aminoglycoside- associated Fanconi's syndrome: an underrecognized entity. Nephron 77: 205-211, 1997 https://doi.org/10.1159/000190274
  7. Katz AI, Doucet A, Morel F. Na-K-ATPase activity along the rabbit, rat, and mouse nephron. Am J Physiol 237: F114-120, 1979
  8. Lee J, Yoo KS, Kang DG, Kim SW, Choi KC. Gentamicin decreases the abundance of aquaporin water channels in rat kidney. Jpn J Pharmacol 85: 391-398, 2001 https://doi.org/10.1254/jjp.85.391
  9. Mahnensmith RL, Aronson PS. The plasma membrane sodium- hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res 56: 773-788, 1985 https://doi.org/10.1161/01.RES.56.6.773
  10. Pastoriza-Munoz E, Bowman RL, Kaloyanides GJ. Renal tubular transport of gentamicin in the rat. Kidney Int 16: 440-450, 1979 https://doi.org/10.1038/ki.1979.149
  11. Preisig PA, Ives HE, Cragoe EJ Jr, Alpern RJ, Rector FC Jr. Role of the Na＋/H＋ antiporter in rat proximal tubule bicarbonate absorption. J Clin Invest 80: 970-978, 1987 https://doi.org/10.1172/JCI113190
  12. Soleimani M, Grassi SM, Aronson PS. Stoichiometry of Na＋-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. J Clin Invest 79: 1276-1280, 1987 https://doi.org/10.1172/JCI112948
  13. Sweet DH. Organic anion transporter (Slc22a) family members as mediators of toxicity. Toxicol Appl Pharmacol 204: 198-215, 2005
  14. Sweet DH, Chan LM, Walden R, Yang XP, Miller DS, Pritchard JB. Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na＋ gradient. Am J Physiol Renal Physiol 284: F763-769, 2003 https://doi.org/10.1152/ajprenal.00405.2002
  15. van Montfoort JE, Hagenbuch B, Groothuis GM, Koepsell H, Meier PJ, Meijer DK. Drug uptake systems in liver and kidney. Curr Drug Metab 4: 185-211, 2003 https://doi.org/10.2174/1389200033489460