title: Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure.
abstract: OBJECTIVE
  The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD).
  
  
  METHODS
  Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.), PTX (100 mg/kg, p.o.), and combination of PTX + ASK once daily for 28 days. We have performed analysis of various renal injury parameters after 4 weeks of treatment.
  
  
  RESULTS
  Treatment with PTX, ASK and combination showed significant improvement in urea, creatinine and total protein in plasma when compared with vehicle treated group in NPX rats. ASK and combination of PTX + ASK elicited significant reduction in blood pressure but PTX alone did not produce blood pressure reduction. ASK treatment showed significant elevation in TNF-alpha, whereas PTX and ASK + PTX showed significant reduction in TNF-alpha in plasma. Histopathologically, the extent of the kidney injury was similar in NPX + vehicle and NPX + ASK-treated rats. PTX and ASK + PTX-treated group showed lesser extent of kidney injury. There was good correlation of mRNA expression levels of kidney injury molecule-1 and bradykinin B1 receptor data with histopathological findings in kidney samples and elevated TNF-alpha levels in plasma.
  
  
  CONCLUSIONS
  We conclude that combination of PTX + ASK may be better therapeutic intervention for nephroprotection in CKD patients.
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, India.
authors.forename: Hitesh M
authors.initials: HM
authors.lastname: Soni
authors.affiliation: Department of Pharmacology, Torrent Pharmaceuticals Ltd, Research Centre, Village-Bhat, Gandhinagar, Ahmedabad, India.
authors.forename: Praful P
authors.initials: PP
authors.lastname: Patel
authors.affiliation: Department of Pharmacology, C. U. Shah College of Pharmacy and Research, Wadhwan, Gujarat, India.
authors.forename: Savan
authors.initials: S
authors.lastname: Patel
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, India.
authors.forename: Akshyaya C
authors.initials: AC
authors.lastname: Rath
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, India.
authors.forename: Aviseka
authors.initials: A
authors.lastname: Acharya
authors.affiliation: Department of Pharmacology, C. U. Shah College of Pharmacy and Research, Wadhwan, Gujarat, India.
authors.forename: Harshkant D
authors.initials: HD
authors.lastname: Trivedi
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, India.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D010431:Pentoxifylline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood; D014508:Urea / Q000097:blood; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D015815:Cell Adhesion Molecules; D003404:Creatinine; D005650:Fumarates; D010431:Pentoxifylline; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D012083:Renin; D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D000092502:Renin Inhibitors; C110936:Havcr1 protein, rat; C446481:aliskiren
keywords: Aliskiren; bradykinin B1 receptor; chronic kidney disease; kidney injury molecule-1; nephroprotection; pentoxyfylline
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