title: Effects of paricalcitol and aliskiren combination therapy on experimental diabetic nephropathy model in rats.
abstract: OBJECTIVE
  The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN) model in rats.
  
  
  METHODS
  Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C), diabetes (Group D), aliskiren (Group A), paricalcitol (Group P), and aliskiren plus paricalcitol (Group A+P) groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 µg/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined.
  
  
  RESULTS
  Group A+P had lower mean albümin-to-creatinine ratio (ACR) (p=0.004) as well as higher creatinine clearance (CCr) (p<0.005) than the diabetic rats (Group D). Combination therapy significantly increased CCr (Group A+P vs. Group A, p<0.005; Group A+P vs. Group P, p=0.022) and reduced ACR (Group A+P vs. Group A, p=0.018; Group A+P vs. Group P, p<0.005) when compared to monotherapy. Serum malondialdehyde levels were significantly lower (p=0.004); glutathion levels (p=0.003), glutathion peroxidase (p=0.004) and superoxide dismutase (p<0.005) activities were significantly higher in group A+P than in group D. The mean scores of mRNA expression of renin (p<0.005), angiotensin II (p=0.012) and angiotensin type 1 receptor (p=0.018) in group A+P were significantly lower. Although combination therapy showed no additional effect on oxidative system, renin-angiotensin system and renal histology, aliskiren plus paricalcitol significantly decreased interstitial fibrosis volume when compared to monotherapy (Group A+P vs. Group A, p<0.005; Group A+P vs. Group P, p=0.002).
  
  
  CONCLUSIONS
  Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.
authors.affiliation: Department of Nephrology, Yeditepe University, Istanbul, Turkey.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Eren
authors.forename: Mehmet Yalçin
authors.initials: MY
authors.lastname: Günal
authors.forename: Elif Arı
authors.initials: EA
authors.lastname: Bakir
authors.forename: Jale
authors.initials: J
authors.lastname: Coban
authors.forename: Berrak
authors.initials: B
authors.lastname: Çağlayan
authors.forename: Nur
authors.initials: N
authors.lastname: Ekimci
authors.forename: Sinem
authors.initials: S
authors.lastname: Ethemoglu
authors.forename: Ozgur
authors.initials: O
authors.lastname: Albayrak
authors.forename: Tuba
authors.initials: T
authors.lastname: Akdeniz
authors.forename: Gülderen Yanikkaya
authors.initials: GY
authors.lastname: Demirel
authors.forename: Ertuğrul
authors.initials: E
authors.lastname: Kiliç
authors.forename: Gülçin
authors.initials: G
authors.lastname: Kantarci
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004872:Ergocalciferols / Q000627:therapeutic use*; D005650:Fumarates / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D000975:Antioxidants; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D005650:Fumarates; C446481:aliskiren; C084656:paricalcitol