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Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats

Authors
Journal
European Journal of Pharmaceutical Sciences
0928-0987
Publisher
Elsevier
Publication Date
Volume
46
Identifiers
DOI: 10.1016/j.ejps.2012.02.002
Keywords
  • Antifibrotic
  • Antiproteinuric
  • Glucose Homeostasis
  • Raas
  • Glomerular Filtration Rate
Disciplines
  • Biology
  • Medicine

Abstract

Abstract The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying the progression of the disease. Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications.

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