| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, United States
2 Medicine-Renal, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
3 Pathology, Instituto Nacional de Ciencias Medicas y Nutricion, SZ, Mexico City, Mexico
4 Harvard Institutes of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
5 , Instituto de Investigaciones Biomedicas, UNAM, Mexico; Dept de Nefrologia y Metabolismo Mineral, Inst Nacional de la Nutrition Salvador Zubiran, Vasco de Quiroga No. 15, Mexico, D.F., Mexico
6 , Instituto de Investigaciones Biomedicas, UNAM, Mexico
* To whom correspondence should be addressed. E-mail: nab{at}biomedicas.unam.mx.
Recent studies from our laboratory have shown that the mineralocorticoid receptor blockade with spironolactone (Sp) prevented renal dysfunction and reduced renal injury in both acute and chronic cyclosporine (CsA) nephrotoxicity. This study was design to evaluate if Sp administration reduces functional and structural renal damage associated with existing chronic CsA nephrotoxicity.
Twenty eight male Wistar rats were fed a low sodium diet. Fourteen received vehicle (V) and the others were treated with CsA (15mg/K sc). After 18 days one half of each group received Sp (20 mg/K p.o.) for the subsequent 18 days. Creatinine clearance, arteriolopathy, tubulo-interstitial fibrosis, arteriolar thickening, glomerular diameter, apoptosis index and TGF-
, procaspase-3 and kidney injury molecule 1 (Kim-1) mRNA levels, as well as Kim-1 shedding in urine were evaluated.
Spironolactone reduced the progression of renal dysfunction and tubulo-interstitial fibrosis in preexisting chronic CsA nephrotoxicity. There was a significant reduction of arteriolar thickening in the CsA+Sp group that was associated with greater glomerular diameter and reduction of apoptosis index. These renoprotective effects were associated with reduction of TGF-, procaspase-3 and Kim-1 mRNA levels as well as Kim-1 shedding into the urine.
In conclusion mineralocorticoid receptor (MR) blockade with spironolactone prevented the progression of renal injury in preexisting chronic CsA nephropathy. These results suggest that spironolactone may reduce CsA-induced established nephrotoxicity in patients.
This article has been cited by other articles:
|
|
 |
|
  J. V. Bonventre Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more Nephrol. Dial. Transplant., November 1, 2009; 24(11): 3265 - 3268. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ramirez, J. Trujillo, R. Valdes, N. Uribe, C. Cruz, G. Gamba, and N. A. Bobadilla Adrenalectomy prevents renal ischemia-reperfusion injury Am J Physiol Renal Physiol, October 1, 2009; 297(4): F932 - F942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Waanders, H. Rienstra, M. W. Boer, A. Zandvoort, J. Rozing, G. Navis, H. van Goor, and J.-L. Hillebrands Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1072 - F1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Trujillo, C. Cruz, A. Tovar, V. Vaidya, E. Zambrano, J. V. Bonventre, G. Gamba, N. Torres, and N. A. Bobadilla Renoprotective mechanisms of soy protein intake in the obese Zucker rat Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1574 - F1582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. T. Nielsen, B. L. Jensen, N. Marcussen, O. Skott, and P. Bie Inhibition of mineralocorticoid receptors with eplerenone alleviates short-term cyclosporin A nephrotoxicity in conscious rats Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2777 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Mathew, H. Patni, A. N. Chaudhary, W. Liang, A. Gupta, P. N. Chander, G. Ding, and P. C. Singhal Aldosterone induces mesangial cell apoptosis both in vivo and in vitro Am J Physiol Renal Physiol, July 1, 2008; 295(1): F73 - F81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Huang, C. Xu, K. W. Kahng, N. A. Noble, W. A. Border, and Y. Huang Aldosterone and TGF-{beta}1 synergistically increase PAI-1 and decrease matrix degradation in rat renal mesangial and fibroblast cells Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1287 - F1295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Iwazu, S. Muto, G. Fujisawa, E. Nakazawa, K. Okada, S. Ishibashi, and E. Kusano Spironolactone Suppresses Peritubular Capillary Loss and Prevents Deoxycorticosterone Acetate/Salt-Induced Tubulointerstitial Fibrosis Hypertension, March 1, 2008; 51(3): 749 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, V. S. Vaidya, R. P. Brown, J. Zhang, B. A. Rosenzweig, K. L. Thompson, T. J. Miller, J. V. Bonventre, and P. L. Goering Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium Toxicol. Sci., January 1, 2008; 101(1): 159 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, B. D. Humphreys, and J. V. Bonventre Shedding of the Urinary Biomarker Kidney Injury Molecule-1 (KIM-1) Is Regulated by MAP Kinases and Juxtamembrane Region J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2704 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, E. A. Bridenbaugh, A. D. Akintola, J. M. Catania, V. S. Vaidya, J. V. Bonventre, A. C. Dearman, H. W. Sampson, D. C. Zawieja, R. C. Burghardt, et al. Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1272 - F1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Patni, J. T. Mathew, L. Luan, N. Franki, P. N. Chander, and P. C. Singhal Aldosterone promotes proximal tubular cell apoptosis: role of oxidative stress Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1065 - F1071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Bobadilla and G. Gamba New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone Am J Physiol Renal Physiol, July 1, 2007; 293(1): F2 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Mejia-Vilet, V. Ramirez, C. Cruz, N. Uribe, G. Gamba, and N. A. Bobadilla Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone Am J Physiol Renal Physiol, July 1, 2007; 293(1): F78 - F86. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
