HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Combination therapy with benazepril and oral adsorbent ameliorates progressive renal fibrosis in uremic rats.

AbstractBACKGROUND/AIMS:
The administration of an angiotensin-converting enzyme (ACE) inhibitor or an oral adsorbent, AST-120 (Kremezin), prevents the progression of renal failure. This study was designed to determine the additional effects of AST-120 combined with an ACE inhibitor, benazepril, on the progression of renal fibrosis in uremic rats.
METHODS:
5/6-nephrectomized uremic rats were divided into control uremic rats (CRF group), benazepril-treated uremic rats (CRF+B group) and uremic rats receiving benazepril and AST-120 (CRF+BK group). After 14 weeks of treatment renal function and pathological changes were investigated.
RESULTS:
The progression of renal dysfunction was delayed in both the CRF+B and CRF+BK groups as compared with the CRF group. In the CRF+BK group, the level of serum and urinary indoxyl sulfate and the tubular accumulation of indoxyl sulfate decreased. Both the CRF+B and CRF+BK groups showed lower glomerular sclerosis indices than the CRF group. In the CRF+BK group, but not the CRF+B group, the interstitial fibrosis area and the expression of transforming growth factor (TGF) beta1 and tissue inhibitor of metalloproteinases (TIMP) 1 were decreased as compared with the CRF group. Furthermore, the CRF+BK group showed a smaller interstitial fibrosis area and a lower renal osteopontin expression than the CRF+B group.
CONCLUSION:
Combination therapy of benazepril and AST-120 is more effective than benazepril alone in retarding the progression of interstitial fibrosis by reducing the expression of TGF-beta 1, TIMP-1 and osteopontin.
AuthorsIsao Aoyama, Kaoru Shimokata, Toshimitsu Niwa
JournalNephron (Nephron) Vol. 90 Issue 3 Pg. 297-312 (Mar 2002) ISSN: 1660-8151 [Print] Switzerland
PMID11867951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2002 S. Karger AG, Basel
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Oxides
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, rat
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Osteopontin
  • Carbon
  • AST 120
  • Indican
  • benazepril
Topics
  • Adsorption
  • Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
  • Animals
  • Benzazepines (therapeutic use)
  • Blood Pressure (physiology)
  • Carbon (therapeutic use)
  • Cells, Cultured
  • Disease Progression
  • Drug Therapy, Combination
  • Fibroblasts (metabolism)
  • Fibrosis
  • Humans
  • In Situ Hybridization
  • Indican (blood, urine)
  • Kidney (drug effects, pathology, physiopathology)
  • Kidney Diseases (drug therapy, pathology, physiopathology)
  • Male
  • Nephrectomy
  • Nephrosclerosis (drug therapy, pathology, physiopathology)
  • Osteopontin
  • Oxides (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins (genetics, metabolism)
  • Tissue Inhibitor of Metalloproteinase-1 (metabolism)
  • Transforming Growth Factor beta (genetics, metabolism)
  • Transforming Growth Factor beta1
  • Uremia (drug therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: