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Rosuvastatin preserves renal structure following unilateral ureteric obstruction in the neonatal rat.
Am J Nephrol. 2012; 35(2):103-13.AJ

Abstract

BACKGROUND/AIMS

Unilateral ureteric obstruction (UUO) in neonatal rodents can be used as a paradigm for in utero obstruction in humans and a platform for studying the potential of novel therapies for congenital obstructive nephropathy. The present study examined the effect of rosuvastatin (Ros) on key morphometric measures of renal injury and corresponding gene expression correlates following neonatal UUO in the rat.

METHODS

Neonatal rats subjected to UUO and controls were treated daily with vehicle or Ros for 14 days. Quantification of tubular dilatation, glomerular size and number and tubulointerstitial fibrotic area was performed and changes validated by reference to appropriate renal gene expression correlates.

RESULTS

UUO increased tubular diameter and interstitial fibrosis by 2.7- and 7-fold, respectively, in parallel with increases in renal transforming growth factor-β(1) (TGF-β(1)) and tumor necrosis factor-α (TNF-α) mRNA levels. Glomerular number and size were reduced by 52 and 33%, respectively. Reductions in WT-1 mRNA and protein expression were noted following obstruction occurring in tandem with reduced mRNA levels for BMP-7 and E-cadherin. Ros attenuated tubular dilatation (33%) and interstitial fibrosis (72%) in association with the normalization of renal TGF-β(1) and TNF-α mRNA levels. Ros improved glomerular number and size (30 and 50%), and preserved mRNA and protein expression levels of WT-1 and normalized mRNA levels for BMP-7 and E-cadherin.

CONCLUSIONS

Ros treatment attenuated all changes, most notably the increase in interstitial fibrosis. Notably, Ros treatment was unable to completely salvage glomerular development. Together these data highlight the therapeutic potential and limitations of Ros in neonatal obstruction.

Authors+Show Affiliations

Áreas de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22212364

Citation

Mazzei, Luciana Jorgelina, et al. "Rosuvastatin Preserves Renal Structure Following Unilateral Ureteric Obstruction in the Neonatal Rat." American Journal of Nephrology, vol. 35, no. 2, 2012, pp. 103-13.
Mazzei LJ, García IM, Altamirano L, et al. Rosuvastatin preserves renal structure following unilateral ureteric obstruction in the neonatal rat. Am J Nephrol. 2012;35(2):103-13.
Mazzei, L. J., García, I. M., Altamirano, L., Docherty, N. G., & Manucha, W. (2012). Rosuvastatin preserves renal structure following unilateral ureteric obstruction in the neonatal rat. American Journal of Nephrology, 35(2), 103-13. https://doi.org/10.1159/000334935
Mazzei LJ, et al. Rosuvastatin Preserves Renal Structure Following Unilateral Ureteric Obstruction in the Neonatal Rat. Am J Nephrol. 2012;35(2):103-13. PubMed PMID: 22212364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rosuvastatin preserves renal structure following unilateral ureteric obstruction in the neonatal rat. AU - Mazzei,Luciana Jorgelina, AU - García,Isabel Mercedes, AU - Altamirano,Liliana, AU - Docherty,Neil G, AU - Manucha,Walter, Y1 - 2011/12/29/ PY - 2011/09/20/received PY - 2011/11/08/accepted PY - 2012/1/4/entrez PY - 2012/1/4/pubmed PY - 2012/6/16/medline SP - 103 EP - 13 JF - American journal of nephrology JO - Am J Nephrol VL - 35 IS - 2 N2 - BACKGROUND/AIMS: Unilateral ureteric obstruction (UUO) in neonatal rodents can be used as a paradigm for in utero obstruction in humans and a platform for studying the potential of novel therapies for congenital obstructive nephropathy. The present study examined the effect of rosuvastatin (Ros) on key morphometric measures of renal injury and corresponding gene expression correlates following neonatal UUO in the rat. METHODS: Neonatal rats subjected to UUO and controls were treated daily with vehicle or Ros for 14 days. Quantification of tubular dilatation, glomerular size and number and tubulointerstitial fibrotic area was performed and changes validated by reference to appropriate renal gene expression correlates. RESULTS: UUO increased tubular diameter and interstitial fibrosis by 2.7- and 7-fold, respectively, in parallel with increases in renal transforming growth factor-β(1) (TGF-β(1)) and tumor necrosis factor-α (TNF-α) mRNA levels. Glomerular number and size were reduced by 52 and 33%, respectively. Reductions in WT-1 mRNA and protein expression were noted following obstruction occurring in tandem with reduced mRNA levels for BMP-7 and E-cadherin. Ros attenuated tubular dilatation (33%) and interstitial fibrosis (72%) in association with the normalization of renal TGF-β(1) and TNF-α mRNA levels. Ros improved glomerular number and size (30 and 50%), and preserved mRNA and protein expression levels of WT-1 and normalized mRNA levels for BMP-7 and E-cadherin. CONCLUSIONS: Ros treatment attenuated all changes, most notably the increase in interstitial fibrosis. Notably, Ros treatment was unable to completely salvage glomerular development. Together these data highlight the therapeutic potential and limitations of Ros in neonatal obstruction. SN - 1421-9670 UR - https://www.unboundmedicine.com/medline/citation/22212364/Rosuvastatin_preserves_renal_structure_following_unilateral_ureteric_obstruction_in_the_neonatal_rat_ L2 - https://www.karger.com?DOI=10.1159/000334935 DB - PRIME DP - Unbound Medicine ER -