Protective Effect of N-Acetylcysteine on Progression of Adriamycin-induced Nephyopathy

  • Han, Sang-Woong (Department of Internal Medicine, Hanyang University College of Medicine) ;
  • Kim, Ho-Jung (Department of Internal Medicine, Hanyang University College of Medicine) ;
  • Paik, Seung-Sam (Department of Pathology, Hanyang University College of Medicine) ;
  • Lee, Jong-Un (Department of Physiology, Chonnam National University Medical School)
  • Published : 2005.06.21


Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) ${\beta}1$ and laminin ${\beta}1$ was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF ${\beta}1$ mRNA and protein, which was ameliorated by NAC. Although the expression of laminin ${\beta}1$ mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF ${\beta}1$.


  1. Border WA, Okuda S, Nakamura T. Extracellular matrix and glomerular disease. Semin Nephrol 9: 307-317, 1989
  2. Van den Branden C, Deman A, Ceyssens B, Pauwels M, Empsen C, Verbeelen D. Vitamin E protects renal antioxidant enzymes and attenuates glomerulosclerosis in adriamycin-treated rats. Nephron 91: 129-133, 2002
  3. Khachigian LM, Collins T, Fries JW. N-acetyl cysteine blocks mesangial VCAM-1 and NF-kappa B expression in vivo. Am J Pathol 151: 1225-1229, 1997
  4. Shu Y, Hoshi S, Tomari S, Watanabe T, Nagata M. Phenotypic changes and cell cycle activation in early tubulointerstitial injury of rat adriamycin nephrosis. Pathol Int 52: 214-223, 2002
  5. Sasaki S, Bao Q, Hughes RC. Galectin-3 modulates rat mesangial cell proliferation and matrix synthesis during experimental glomerulonephritis induced by anti-Thy1.1 antibodies. J Pathol 187: 481-489, 1999<481::AID-PATH263>3.0.CO;2-2
  6. Tamaki K, Okuda S, Ando T, Iwamoto T, Nakayama M, Fujishima M. TGF-$\beta$1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy. Kidney Int 45: 525-536, 1994
  7. Manabe N, Kinoshita A, Yamaguchi M, Furuya Y, Nagano N, Yamada-Uchio K, Akashi N, Miyamoto-Kuramitsu K, Miyamoto H. Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy. J Vet Med Sci 63: 125-133, 2001
  8. Rangan GK, Wang Y, Tay YC, Harris DC. Inhibition of nuclear factor-B activation reduces cortical tubulointerstitial injury in proteinuric rats. Kidney Int 56: 118-134, 1999
  9. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 6: 593-597, 1989
  10. Nath KA, Grande J, Croatt A, Haugen J, Kim Y, Rosenberg ME. Redox regulation of renal DNA synthesis, transforming growth factor-1 and collagen gene expression. Kidney Int 53: 367-381, 1998
  11. Okasora T, Takikawa T, Utsunomiya Y, Senoh I, Hayashibara H, Shiraki K, Kasagi T, Shimizu F. Suppressive effect of superoxide dismutase on adriamycin nephropathy. Nephron 60: 199-203, 1992
  12. Barbey MM, Fels LM, Soose M, Poelstra K, Gwinner W, Bakker W, Stolte H. Adriamycin affects glomerular renal function: evidence for the involvement of oxygen radicals. Free Radic Res Commun 7: 195-203, 1989
  13. Shah SV. Role of reactive oxygen metabolites in experimental glomerular disease. Kidney Int 35: 1093-1106, 1989
  14. Horikoshi S, Ebihara I, Nakamura T, Koide H. Abnormal distribution of masangium-specific laminin in glomeruli of patients with idiopathic membranous nephropathy. Nephron 81: 284-288, 1999