These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Rho kinase inhibition by fasudil attenuates cyclosporine-induced kidney injury.
    Author: Park JW, Park CH, Kim IJ, Bae EH, Ma SK, Lee JU, Kim SW.
    Journal: J Pharmacol Exp Ther; 2011 Jul; 338(1):271-9. PubMed ID: 21474569.
    Abstract:
    It has been shown that the inhibition of the Rho/Rho kinase (ROCK) pathway prevents tubulointerstitial fibrosis and ameliorates renal function in various progressive renal disorders. The present study was to determine whether fasudil, a ROCK inhibitor, has a protective effect on cyclosporine A (CsA)-induced nephropathy. Male Sprague-Dawley rats were treated with CsA (n = 10, 20 mg · kg(-1) day(-1) s.c.), CsA + fasudil (n = 10, 3 mg · kg(-1) day(-1) i.p.), or vehicle alone (n = 10) for 28 days. Fasudil cotreatment ameliorated CsA-induced changes and restored renal function. CsA decreased the expression of endothelial nitric-oxide synthase and increased inducible nitric-oxide synthase/3-nitrotyrosine in the kidney. Accordingly, there was infiltration of inflammatory cells and up-regulation of inflammatory cytokines. Fasudil also significantly suppressed the expression of transforming growth factor-β1, Smad signaling, and subsequent epithelial-to-mesenchymal processes. In addition, fasudil augmented p27(kip1) expression and decreased the number of proliferating cell nuclear antigen-positive cells. In another series of experiments using HK-2 cells in culture, fasudil also suppressed CsA-induced increases in mitogen-activated protein kinase phosphorylation. CsA induced expression of p53, the degree of which was attenuated by fasudil in association with decreases of proapoptotic markers such as Bad, Bax, and total/cleaved caspase-3. These results suggest that inhibition of the Rho/ROCK pathway attenuates CsA-induced nephropathy through the suppression of the induction of inflammatory, apoptotic, and fibrogenic factors, along with inhibition of Smad, mitogen-activated protein kinases, and nitric oxide signaling pathways.
    [Abstract] [Full Text] [Related] [New Search]